AAV-mediated expression of p65shRNA and bone morphogenetic protein 4 synergistically enhances chondrocyte regeneration

BACKGROUND:Adeno-associated virus(AAV)gene therapy has been proven to be reliable and safe for the treatment of osteoarthritis in recent years.However,given the complexity of osteoarthritis pathogenesis,single gene manipulation for the treatment of osteoarthritis may not produce satisfactory results.Previous studies have shown that nuclear factorκB could promote the inflammatory pathway in osteoarthritic chondrocytes,and bone morphogenetic protein 4(BMP4)could promote cartilage regeneration.OBJECTIVE:To test whether combined application of AAV-p65shRNA and AAV-BMP4 will yield the synergistic effect on chondrocytes regeneration and osteoarthritis treatment.METHODS:Viral particles containing AAV-p65-shRNA and AAV-BMP4 were prepared.Their efficacy in inhibiting inflammation in chondrocytes and promoting chondrogenesis was assessed in vitro and in vivo by transfecting AAV-p65-shRNA or AAV-BMP4 into cells.The experiments were divided into five groups:PBS group;osteoarthritis group;AAV-BMP4 group;AAV-p65shRNA group;and BMP4-p65shRNA 1:1 group.Samples were collected at 4,12,and 24 weeks postoperatively.Tissue staining,including safranin O and Alcian blue,was applied after collecting articular tissue.Then,the optimal ratio between the two types of transfected viral particles was further investigated to improve the chondrogenic potential of mixed cells in vivo.RESULTS AND CONCLUSION:The combined application of AAV-p65shRNA and AAV-BMP4 together showed a synergistic effect on cartilage regeneration and osteoarthritis treatment.Mixed cells transfected with AAV-p65shRNA and AAV-BMP4 at a 1:1 ratio produced the most extracellular matrix synthesis(P<0.05).In vivo results also revealed that the combination of the two viruses had the highest regenerative potential for osteoarthritic cartilage(P<0.05).In the present study,we also discovered that the combined therapy had the maximum effect when the two viruses were administered in equal proportions.Decreasing either p65shRNA or BMP4 transfected cells resulted in less collagen II synthesis.This implies that inhibiting inflammation by p65shRNA and promoting regeneration by BMP4 are equally important for osteoarthritis treatment.These findings provide a new strategy for the treatment of early osteoarthritis by simultaneously inhibiting cartilage inflammation and promoting cartilage repair.

Anti-inflammatory Activity of Berbamine

Berbamine, a kind of alkaloid, was studied for anti-inflammatory activity. Thedrug was tested on carrageenan-induced rat paw oedema and kaolin-induced arthritis in rats.Berbamine has shown significant anti-inflammatory and anti-arthritic activities.

IMMUNOLOGICAL STUDY ON ACUPUNCTURE TREATMENT OF COLLAGEN-INDUCED ARTHRITIS IN CX43-KNOCK-OUT RATS

Objective To observe the therapeutic effect of acupuncture for collagen-induced arthritis （CIA） in Cx43 knock-out mice and its underlying immunological mechanism.Methods Heterozygote （Cx43^＋/-） mice （n=64） and wild-type （Cx43^＋/＋） mice （n=46） were used in the present study.CIA model was es- tablished by intracutaneous injection of bovine collagenⅡ（immunonization）.Acupuncture of Zúsānlǐ（足三里ST36） was carried out from the 4^th week on after the initial immunization,once a day for 3 weeks.Arthritis score and days of onset of CIA were recorded.Intracellular contents of Th subgroups of splenic lymphocytes were detected with flow cytometry.Results The incidence rate of CIA and arthritis score in Cx43^＋/- mice were significantly lower than those in Cx43^＋/＋ mice （P〈0.05）.In Cx43^＋/＋ mice,3 weeks after acupuncture treatment,the score of arthritis symptoms and signs in acupuncture group was significantly lower than that in model group （P〈0.01）,while in Cx43^＋/- mice,no significant difference was found between model group and acupuncture group in arthritis score （P〉0.05）.In comparison with control group,percentages of both Thl and Th2 and Th1/Th2 increased significantly in 0x43^＋/＋ CIA model group （P〈0.05）,while compared with model group,the percentage of Th1,Th2 and Th1/Th2 in acupuncture group decreased evidently （P〈0.05） or moderately,showing that acupuncture can effectively suppress arthritis-induced increase of Thl in Cx43^＋/＋ mice.In 0x43^＋/- mice,Th1 level and Th1/Th2 of CIA model group increased considerably in comparison with control group （P〈0.05）,while compared with model group,the Th1,Th2 and Th1/Th2 of acupuncture group had no significant changes （P〉0.05）,indicating that the effect of acupuncture in suppressing increase of Th1 percent and Th1/Th2 was eliminated.Conclusion Acupuncture of Zúsānlǐ（足三里ST 36） can effectively relieve CIA symptoms and signs and inhibit increase of splenic Th1 in Cx43^＋/＋ mice but has no any effect on CIA score,Th1,Th2 and Th1/Th2 in Cx43^＋/- mice.It shows the effect of acupuncture in improving CIA is closely related to Cx43 gene.

Inhibiting Effect of Lobenzarit Disodium on the Inter-leukin-1 Activity in Normal and in Adjuvant ArthritisKats and on the H_2O_2 Release from Rat Peritoneal Macro-phages

The effects of Lobenzarit disodium (CCA) upon the activity of interleukin-1(IL-1) of peritoneal macrophages(PMΦ)in normal and in adjuvant arthritis AA) rats and on the release of hydrogen peroxide(H_2O_2)of rat peritoneal macrophages were studied. CCA 10～200 μg/ml could inhibit IL-1activity in normal rat in vitro;CCA 10 and 50 mg/kg could depress the level of increased IL-1 in AA rats in vivo;CCA 5～100μg/ml could inhibit the release of H_2O_2 from rat PMΦin vitro.The results suggest that these effects could be one of the mechanisms of anti-inflammatory action of CCA.

FORTY-EIGHT CASES OF ACUTE GOUTY ARTHRITIS TREATED COMPREHENSIVELY WITH ELECTROACUPUNCTURE AND WARMING MOXIBUSTION

Objective To probe into the effects on acute gouty arthritis treated comprehensively with electroacupuncture (EA) and warming moxibustion. Methods 70 cases were randomized into treatment group (48 cases), in which the EA+warming moxibustion was applied; and controlled group (22 cases), in which, colchicine was prescribed for oral administration. Results The statistical outcomes after 1 course treatment in treatment group: 28 cases were cured (58.33%), 18 cases improved (37.50%) and the total effective rate was 95.83%. In controlled group: 12 cases (54.55%) were cured, 8 cases improved (36.36%) and the total effective rate was 90.91%. The therapeutic effects of two groups were basically consistent, without significant different (P>0.05). But, concerning to side effect, there was no any toxic side effects in the group treated with EA+warming moxibustion, and the occurrence rate in the group treated with colchicine was 40.91%. Conclusion Electroacupuncture+warming moxibustion achieves good therapeutic effects without any side effects.

Altered Gene Expression in Articular Chondrocytes of Smad3^(ex8/ex8) Mice, Revealed by Gene Profiling Using Microarrays

It has been previously reported that small mother against decapentaplegic 3 （Smad3） gene knockout （Smad3^ex8/ex8） mice displays phenotypes similar to human osteoarthritis, as characterized by abnormal hypertrophic differentiation of articular chondrocytes. To further clarify the crucial target genes that mediate transformation growth factor-β （TGF-β）/Smad3 signals on articular chondrocytes differentiation and investigate the underlying molecular mechanism of osteoarthritis, microarrays were used to perform comparative transcriptional profiling in the articular cartilage between Smad3^ex8/ex8and wild-type mice on day five after birth. The gene profding results showed that the activity of bone morphogenetic protein （BMP） and TGF-β/cell division cycle 42 （Cdc42） signaling pathways were enhanced in Smad3^ex8/ex8 chondrocytes. Moreover, there was altered gene expression in growth hormone/insulin-like growth factor 1 （Igfl） axis and fibroblast growth factor （Fgf） signaling pathway. Notably, protein synthesis related genes and electron transport chain related genes were upregulated in Smad3^ex8/ex8 chondrocytes, implying that accelerated protein synthesis and enhanced cellular respiration might contribute to hypertrophic differentiation of articular chondrocytes and the pathogenesis of osteoarthritis.

Effect of Osteoarthritis Patients' Gender on Rehabilitation after Total Knee Arthroplasty

Objective To investigate the influence of gender on osteoarthritic knee rehabilitation outcome of osteoarthritis patient undergoing total knee arthroplasty(TKA).Methods We prospectively studied thirty male and thirty female knee primary osteoarthritis patients receiving unilateral TKA with posterior stable-fixed plateau prosthesis at our hospital from March 2003 to March 2008.The age and body mass index of male and female patients were matched.The surgical and rehabilitation clinical factors were compared between two groups.Results There was no significant difference in postoperative hospitalization time,surgical tourniquet time,and wound drainage volume between two groups(P>0.05).The extension/flexion degrees of knee joint before operation,1-week,2-week and 1-year after operation for male patients were 6.0 ± 3.3 degrees/ 114.0 ± 10.0 degrees,2.0 ± 1.6 degrees/93.0 ± 7.4 degrees,0.6 ± 0.6 degrees/104.0 ± 9.9 degrees and 0.3 ± 0.5 degrees/125.0 ± 8.8 degrees,for female patients were 7.0 ± 3.4 degrees/112.0 ± 14.0 degrees,2.0 ± 1.3 degrees/89.0 ± 10.9 degrees,0.9 ± 0.8 degrees/101.0 ± 11.8 degrees,0.4 ± 0.5 degrees/124.0 ± 7.1 degrees.The range of motion before operation,1-week,2-week,and 1-year after operation for male patients was 108.0 ± 9.5 degrees,91.0 ± 7.1 degrees,103.0 ± 9.9 degrees,and 125.0 ± 8.9 degrees,for female patients was 105.0 ± 14.1 degrees,87.0 ± 11.4 degrees,100.0±11.9 degrees,and 124.0 ± 7.0 degrees.The preoperative and 1-year postoperative HSS scores were 55.8 ± 13.3 and 89.6 ± 6.7 for males and 54.5 ± 13.8 and 89.2 ± 4.1 for females.No significant statistical difference was observed between two gender groups in regards to degree of extension and flexion,range of motion and HSS score(P>0.05).Conclusions Gender does not influence postoperative knee function of osteoarthritis patients.TKA significantly improves knee joint function and relieve osteoarthritis-related pain.

Acute pancreatitis in aging animals:Loss of pancreatitis-associated protein protection?

AIM:To investigate the effect of age on severity of acute pancreatitis(AP) using biochemical markers,histology and expression of the protective pancreatitisassociated proteins(PAPs).METHODS:AP was induced via intraductal injection of 4% sodium taurocholate in young and old rats.Sera and pancreata were assayed at 24 h for the parameters listed above;we also employed a novel molecular technique to assess bacterial infiltration using polymerase chain reaction to measure bacterial genomic ribosomal RNA.RESULTS:At 24 h after induction of AP,the pancreata of older animals had less edema(mean ± SE histologic score of young vs old:3.11 ± 0.16 vs 2.50 ±-0.11,P < 0.05),decreased local inflammatory response(histologic score of stromal infiltrate:3.11 ± 0.27 vs 2.00 ± 0.17,P < 0.05) and increased bacterial infiltration(174% ± 52% increase from sham vs 377% ± 4%,P < 0.05).A decreased expression of PAP1 and PAP2 was demonstrated by Western blotting analysis and immunohistochemical staining.There were no differences in serum amylase and lipase activity,or tissue myeloperoxidase or monocyte chemotactic protein-1 levels.However,in the most-aged group,serum C-reactive protein levels were higher(young vs old:0.249 ± 0.04 mg/dL vs 2.45 ± 0.68 mg/dL,P < 0.05).CONCLUSION:In older animals,there is depressed PAP expression related to a blunted inflammatory response in AP which is associated with worsened bacterial infiltration and higher C-reactive protein level;this may explain the more aggressive clinical course.

Treatment of 60 Cases of Gouty Arthritis with Modified Simiao Tang

Objective:To observe the clinical effect of a modified Simiao Tang (加味四妙汤 Modified Decoction of Four Wonderful Drugs) for gouty arthritis and its influence on uric acid in blood. Methods: 120 cases of gouty arthritis were randomly divided into the treatment group and control group with 60 cases in each group. Modified Simiao Tang (MST) was orally administered to the patients in the treatment group and allopurinol tablet was orally administered to the patients in the control group. The clinical effects of two groups were evaluated after one-week treatment and uric acid (UA) and C-reactive protein (CRP) levels in blood were determined after 1-month treatment. Results: The total effective rate in the treatment group was significantly higher than in the control group, 86.7% vs. 68.3% (P< 0.01). And the treatment group was also significantly better than the control group in decreasing UA and CRP (P<0.05 or P<0.01). Conclusions: MST can significantly improve the symptoms and signs of gouty arthritis and decrease the levels of UA and CRP. It is good for gouty arthritis.

Regenerative Engineering for Knee Osteoarthritis Treatment： Biomaterials and Cell-Based Technologies

Knee osteoarthritis （OA） is the most common form of arthritis worldwide. The incidence of this disease is rising and its treatment poses an economic burden. Two early targets of knee OA treatment include the predominant symptom of pain, and cartilage damage in the knee joint. Current treatments have been beneficial in treating the disease but none is as effective as total knee arthroplasty （TKA）. However, while TKA is an end-stage solution of the disease, it is an invasive and expensive procedure, Therefore, innovative regenerative engineering strategies should be established as these could defer or annul the need for a TKA. Several biomaterial and cell-based therapies are currently in development and have shown early promise in both preclinical and clinical studies. The use of advanced biomaterials and stem cells independently or in conjunction to treat knee OA could potentially reduce pain and regenerate fo- cal articular cartilage damage. In this review, we discuss the pathogenesis of pain and cartilage damage in knee OA and explore novel treatment options currently being studied, along with some of their limitations.

Curcumin inhibits hepatitis B virus infection by downregulating ccc DNA-bound histone acetylation

AIM To investigate the potential effect of curcumin on hepatitis B virus(HBV) covalently closed circular DNA(ccc DNA) and the underlying mechanism.METHODS A Hep G2.2.15 cell line stably transfected with HBV was treated with curcumin, and HBV surface antigen(HBs Ag) and e antigen(HBe Ag) expression levels were assessed by ELISA. Intracellular HBV DNA replication intermediates and ccc DNA were detected by Southern blot and real-time PCR, respectively. The acetylation levels of histones H3 and H4 were measured by Western blot. H3/H4-bound ccc DNA was detected by chromatin immunoprecipitation(Ch IP) assays. The deacetylase inhibitors trichostatin A and sodium butyrate were used to study the mechanism of action for curcumin. Additionally, short interfering RNAs(si RNAs) targeting HBV were tested along with curcumin.RESULTS Curcumin treatment led to time-and dose-dependent reductions in HBs Ag and HBe Ag expression and significant reductions in intracellular HBV DNA replication intermediates and HBV ccc DNA. After treatment with 20 μmol/L curcumin for 2 d, HBs Ag and ccc DNA levels in Hep G2.2.15 cells were reduced by up to 57.7%(P < 0.01) and 75.5%(P < 0.01), respectively, compared with levels in non-treated cells. Meanwhile, time-and dose-dependent reductions in the histone H3 acetylation levels were also detected upon treatment with curcumin, accompanied by reductions in H3-and H4-bound ccc DNA. Furthermore, the deacetylase inhibitors trichostatin A and sodium butyrate could block the effects of curcumin. Additionally, transfection of si RNAs targeting HBV enhanced the inhibitory effects of curcumin.CONCLUSION Curcumin inhibits HBV gene replication via downregulation of ccc DNA-bound histone acetylation and has the potential to be developed as a ccc DNA-targeting antiviral agent for hepatitis B.

Development of ulcerative colitis during the course of rheumatoid arthritis: Association with selective IgA deficiency

A 56-year-old woman with a 29-year history of rheumatoid arthritis （RA） was admitted to the hospital, complaining of high fever, abdominal pain and severe bloody diarrhea. Colonoscopy revealed friable and edematous mucosa with spontaneous bleeding, diffuse erosions and ulcers extending from the rectum to the distal transverse colon. Histopathological findings of rectal biopsies were compatible with ulcerative colitis （UC）. Being diagnosed as having severe active leftside UC, she was successfully treated with intravenous methylprednisolone followed by prednisolone and leukocytapheresis. Laboratory tests revealed low serum and saliva IgA levels, which might play a role in the development of UC. To our knowledge, this is the first case of UC occurring during the course of RA, accompanied by selective IgA deficiency.

Influencing factors analysis of spontaneous knee joint osteoarthritis among middle aged and old aged pople in Xi'an

Objective:To explore the prevalence rate of knee joint osteoarthritis and its pathogenetic fea- tures among the middle-aged and old aged people in the urban and rural area of Xi'an.Methods:From May to October 2005,1538 Han nationality above 40 years in Xi'an were investigated according to strati- fied and cluster random sampling.The same questionnaire was delivered to subjects who had been given normotopia and lateral position radiographic examination in both knees.Excluded from etiological arthri- tis,some subjects with clinical symptoms and a radiographic grade (beyond Kellgren & Lawrence gradeⅡ) were finally diagnosed as spontaneous knee joint osteoarthritis.All analyses were performed with SPSS 13.0 and t test,U test.Single factor analysis and multiple logistic regression analysis were used to analyze dates.Results:The total prevalence of spontaneous knee joint osteoarthritis was 12.1% with 2.5% and 2.1% for right and left knees,respectively.The prevalence of knee joint osteoarthritis in wom- en was 2.5 times of that in men (17.2% vs 6.8%,P=0.000).the osteophyte prevalence in women was 2.3 times of that in men (26.5% vs 11.4%,P=0.000).The prevalence of knee joint osteoarthritis and osteophyte increased with the growth of age.So did the symptomatic knee,except for the age group of 56- 60 years and 66-70 years.The prevalence of symptomatic knee joint for urban area was significantly higher than that for rural area (56.3% vs 45.3%,P=0.003).In women,the prevalence of knee joint os- teoarthritis increased significantly with the increasing of body mass index,which had not been observed in men.Female and obesity are the risk factors for osteoarthritis,but bean and its products and meat could prevent the osteoarthritis.Conclusion:Old age,female and obesity serve as risk factors for knee joint os- teoarthritis.

The effects of total ankle replacement on ankle joint mechanics during walking

Background:End-stage ankle arthritis impairs joint function and patients' mobility.Total ankle replacement is a surgical procedure to treat severe ankle arthritis.Salto Talaris Anatomic Ankle^(TM)(STAA) was designed to mimic the normal ankle anatomy and flexion/extension of the ankle movement.The purpose of this study was to examine the effect of an STAA ankle replacement on ankle joint function and mechanics during gait.Methods:Five patients with end-stage unilateral ankle arthritis were recruited.Patients performed level walking in a laboratory setting on 2occasions,prior to and 3 months after the STAA ankle surgeries.American Orthopedic Foot and Ankle Society(AOFAS) hindfoot score was obtained.A 12-camera motion capture system was used to perform walking analysis.Gait temporo-spatial parameters and ankle joint mechanics were evaluated.Paired Student's t tests and non-parametric Wilcoxon matched tests were performed to examine the differences in biomechanical variables between the pre-and post-surgery walking conditions.Results:Compared to the pre-surgical condition,at 3 months of post-STAA surgery,patients experienced greater improvement in AOFAS hindfoot score(p = 0.0001);the STAA ankle demonstrated a 31% increase in ankle joint excursion(p = 0.045),a 22% increase in ankle plantarflexor moment(p = 0.075),a 60% increase in ankle power absorption(p = 0.023),and a 68% increase in ankle power production(p = 0.039).Patients also demonstrated a 26% increase in walking speed(p = 0.005),a 20% increase in stride length(p = 0.013),a 15% decrease in double support time(p = 0.043),and a 5% decrease in total stance time(p = 0.055).Conclusion:Three months after surgeries,the STAA patients experienced improvements in ankle function and gait parameters.The STAA ankle demonstrated improved ankle mechanics during daily activities such as walking.

Factors associated with balance function in patients with knee osteoarthritis:An integrative review

This integrative review is to identify the factors associated with balance function in patients with knee osteoarthritis and explore the relationship between these factors and balance function.Osteoarthritis commonly occurs in elderly people.Patients with knee osteoarthritis have balance impairment,and maintaining knee stability is important for such patients to prevent accidental injuries caused by falling.Therefore,it is important to clarify the factors related to balance function in patients with knee osteo-arthritis.The PubMed,Science Direct,CINAHL,Ovid,ProQuest,CNKI,WanFang databases were searched,and relevant articles published up to December 2015 were included.Twenty articles were included in the analysis.Age,gender,dominant limb,foot length,knee alignment,diurnal variation,and meniscus tears were the non-modifiable factors,whereas body mass index,knee pain,muscle strength,joint range of motion,severity,and cognitive loading were the modifiable factors.Knee sleeve and custom-molded insoles showed protective effects against knee osteoarthritis.

Safety evaluation on the clinical application of Tenghuangjiangu tablet for osteoarthritis:a hospital registration study

To evaluate the treatment safety of Tenghuangjiangu tablet on osteoarthritis,3365 osteoarthritis patients whose prescription included Tenghuangjiangu tablet from 15 hospitals were involved in the prospective and multi-center clinical trial.Tenghuangjiangu tablet dosage was decided by instruction or doctors’experience.The course of treatment and observation was 4 weeks.The adverse drug reactions were observed in the treatment process.Results showed male and female patients were 1018(30.25%)and 2347(69.75%),respectively,and 528 patients had allergic history.The patients’average age was 58.30±8.99 years,and the average disease course was 33.29±37.40 months.The average score of WOMAC scale was 95.07±42.42,which indicated the light conditions.2275 patients were treated with combined drug regimen.There were two adverse drug reactions in this research.One reaction was skin rashes with itching and the interventions were stopped original drugs and give antianaphylactic treatment.The other reaction was stomach discomfort with disgusting and the intervention was stopped the original drugs temporarily,then continued to take two drugs after 3 days and the reaction didn’t appear.The accident rate of adverse drug reaction was 0.059%.The safety of Tenghuangjiangu tablet clinical application was good,and the mechanism of adverse drug reaction should be researched in-depth.

Gastrointestinal lesions associated with spondyloarthropathies

Subclinical gut inflammation has been described in up to twothirds of patients with spondyloarthropathies(SpA).Arthritis represents an extraintestinal manifestation of several gastrointestinal diseases, including inflammatory bowel disease(IBD), Whipple's disease, Behcet's disease, celiac disease, intestinal bypass surgery, parasitic infections of the gut and pseudomembranous colitis.Moreover about two thirds of nonsteroidal antiinflammatory drug users demonstrate intestinal inflammation.Arthritis may manifest as a peripheral or axial arthritis.The spondyloarthropathy family consists of the following entities:ankylosing spondylitis, undifferentiated spondyloarthritis, reactive arthritis, psoriatic arthritis, spondyloarthritis associated with IBD, juvenile onset spondyloarthritis.This topic reviews the major gastrointestinal manifestations that can occur in patients with SpA and in nonsteroidal anti inflammatory drugs users.

Expression of CC Chemokine Ligand 5 in Patients with Rheumatoid Arthritis and Its Correlation with Disease Activity and Medication

Objective To determine the levels of CC chemokine ligand 5 (CCL5) in serum and synovial fluid (SF) from patients with rheumatoid arthritis (RA) and their relations with disease activity and medication. Methods CCL5 in serum and SF was quantified by enzyme-linked immunosorbent assay (ELISA) in 28 RA patients and 21 osteoarthritis (OA) patients. In RA patients, the correlations of CCL5 levels in serum and SF with disease activity were analyzed. Meanwhile, the serum CCL5 levels among RA patients treated with disease-modifying antirheumatic drugs (DMARDs), Tripterygium Glucosides, and other Chinese herbs without disease-modifying effects were also compared. Results CCL5 levels in both serum and SF of RA patients were significantly higher than those of OA patients (P<0.05). Moreover, the level of CCL5 was higher in SF than that in serum of RA patients (P<0.01). Serum CCL5 level was correlated significantly with the number of swollen joints (r=0.3329, P<0.05), erythrocyte sedimentation rate (r=0.4001, P<0.05), and C reactive protein (r=0.3735, P<0.01). In addition, the level of CCL5 had a trend of lower in patients treated with DMARDs or Tripterygium Glucosides than those treated with other Chinese herbs, although the difference was not significant among those patients due to the small number of patients in each group. Conclusions In RA patients, the expression of CCL5 increases and correlates with some clinical and laboratory parameters of RA, which indicate that CCL5 plays an important role in RA and may serve as a useful marker of disease activity. DMARDs and Tripterygium Glucosides might exert their clinical effects through reducing CCL5 production in RA.

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.