Patient Presentation

1. Patient Presentation • 29 Male • Presenting complaint • Painful elbow and ankle • Pain character • 2weeks • Pain seems to be inside the joints • Stiff feeling – improves with activity • Worse in mornings after get out of bed and when standing up after sitting for a while • Not the first episode of joint pain • Joint pain migrates • No family history of joint diseases • No chronic medical conditions

2. Patient Presentation • Activity history • Recently changed his job • Sitting mostly • Moderately active (especially squash) • Injury history • No history of injuries • Nutrition history • Avoids some foods as it causes GIT symptoms • Grains etc.

3. Physical examination • Unremarkable • FROM, 5/5 Power • No swelling / deformities • No signs of inflammation • Biomechanics • NAD • Two cannibals are eating a clown. One says to the other: "Does this taste funny to you?"

4. Differential diagnosis • Bursitis • Tendinopathy • Osteoarthritis • Auto-immune disorders • Etc. etc. etc.

5. Special investigations • X-rays – NAD • Bloods (RF, ANF, Uric acid) – NAD • Ultrasound – NAD • Being part of the human race does not count as exercise.

6. Follow-up visit • Asked again about pain • Not associated with increased activity levels • Joint pains does seem to present in at least 2 joints • When asked about previous episode of joint pains it emerges that: • During his final exams at varsity • On further inquiry into any other inflammatory symptoms or conditions • He finally admits he was previously diagnosed with Ulcerative Colitis. • On and off on Salazopyrin

7. 3 Step Summary • Clinical • Ulcerative colitis • Stress induced his flare ups • Then develops arthropathy symptoms • Personal • Shame associated with diagnosis • Contextual • Job change – stress • Trying to fall pregnant stress

8. Problem list • Active • Unmanaged UC • Chronic meds • Specialist follow-up - long overdue • Passive • Not on structured diet & exercise program • Infertility related to drugs

9. Plan • Referred for gastroenterologist follow-up • Changed meds • Referred for specialist dietician consult • Worked out an exercise program with goals • Did you hear about the blind circumciser? He got the sack.

10. Progression • Completely symptom free • Exercise program showing good results • Fertility? • My doctor found a new surefire diagnosis fior erectile dysfunction. It wasn't hard.

11. The joint-gut axis in inflammatory bowel diseases. R. De Wet September 2012

12. Introduction • UC & CD are both part of the Ideopathic Bowel Disease • Are chronic diseases with a relapsing and remitting clinical course • The precise etiology is still unknown and therefore a causal treatment is not yet available. • Incidence = 0.5% of the population • Onset = 20-29yrs

13. Chron’s vs. Ulcerative colitis

14. Extraintestinal manifitations of IBD • Liver • Fatty change, primary sclerosing cholangitis, pericholangitis • Skin • Erythema nodosum, pyoderma gangrenosum, Aphtous ulceration, Sweet’s syndrome (esp. Chron’s) • Eyes • Episcleritis, anterior uveitis • Joints • As discussed • Systemic • Amyloidosis • Other • Thrombosis, pericarditis, lung-disease, nephro- / cholelithiasis

15. Inflammatory bowel diseases (Crohn's disease and ulcerative colitis), are associated with a variety of extraintestinal manifestations. • Most common = Articular involvement (16% to 33%)

16. Pathology of UC & CD • Pathogenetic mechanism is largely unclear • The generally accepted theory = A combination of • Environmental factors or agents • Dysfunctional mucosal immunity • In a genetically susceptible individual • Natural history of IBD is characterised by flares & remissions and a also a general alteration in gut permeability

17. Introduction • In 1930 Bargen first described the relationship between IBS and arthritis • At that stage thought it was due to rheumatoid arthritis • After the Rose-Waaler agglutination test- ‘colitic arthritis’ was used • Hey, I'm still maintaining last year's New Years resolution of one sit-up per day - getting out of bed.

18. Van der Broek in 1988 showed a cross reactivity between gut bacteria and cartilage • In a study by Leirisalo, he did colonoscopies on 118 patients with inflammatory and non-inflammatory joint diseases and found endoscopic lesions in 44% of patients (26% CD) • They found there is a sharing of certain peptides by colonic epithelium, cilliary process of the eye and chondrocytes of the joints

19. Pathogenesis • There are several arguments in favour of an important role the intestinal mucosa has in the development of spondylo-arthropathies • Genetics doesn’t seem important in spondylitis with IBD • The role of bacterial antigens = important • I read an article last night about the dangers of heavy drinking, really scared the sh*t out of me... So that's it, I've decided from today on, no more reading.

20. Classification of Enteropathic arthritis • Infective- / Reactive arthritis • Shigella, salmonella etc. • Spondyloarthrpathies in IBD’s • Other spondyloarthropathies include • Reactive- and psoriatric arthritis, ankylosing spondylitis: juvenile & adult form (more in UC) • Other • Ileojejenal bypass, coeliac disease, Whippel’s disease

21. Arthritis associated with inflammatory bowel diseases is one of the diseases captured under the umbrella of spondyloarthritis. • Spondyloarthritis is a group of inflammatory diseases with overlapping features (e.g. psoriasis, uveitis and IBD) and is linked to Human Leukocyte Antigen-B27.

22. Criteria for Spondylo-arthropathies diagnosis • European Spondyloarthropathy Study Group criteria for Spondylo-arthropathies diagnosis (77%sensitivity & 89% specificity) – 18.5% of IBD will be positive • Inflammatory spinal pain or synovitis (assymetric, predominantly in the lower limbs) and any one of the following • Positive family history • Psoriasis • IBD • Alternate but pain • Enthesopathy UC and Chrons localized to the colon - seems to be more associated with Spondyloarthropathies

23. Presentation • Arthropathy in inflammatory bowel diseases is clinically divided into: • Peripheral and • Often flares with relapses of bowel disease • Axial involvement. • Course is independent of inflammatory bowel disease activity. • How do you get a fat bird in to bed? Piece of cake.

24. Pathology of Spondyloarthropathies • Naive lymphocytes recirculate between the blood and lymphoid tissues in search of antigens that are transported to the immune system via the gut epithelium • They translocate through specific epithelial cells of the intestine, the M-cells, into • underlying Peyer's patches (secondary lymphoid tissue). • The lymphocyte recirculation directs naive lymphocytes into the Peyer's patches by recognizing the endothelial lining of high endothelial venules • (HEVs, specialized postcapillary venules).

25. When a lymphocyte finds an antigen, processed by professional antigen presenting cells, • the cell becomes activated within the • Germinal centres (B cell) or • Outside the centres (T cell) in mesenteric lymph nodes, • Starts to proliferate and differentiate and return to the systemic circulation via the efferent lymphatic system. • Following imprinting, the activated mucosal immunoblast goes back to the lamina propria of the gut, where it exerts its effector functions.

26. With inflammation, changes occur in the mucosal vasculature, including • vasodilatation, hyperaemia and increased permeability of the vessel wall, which are induced by • The release and actions of various inflammatory mediators, • This results in enhanced extravasation of leukocytes. • Furthermore, the migration pathways of lymphocytes are altered by expression patterns of adhesion molecules and chemokines, • and these may provide an explanation for the pathogenesis of some extraintestinal manifestations in IBD.

27. Do intestinal lymphocytes traffic to the joints? • Studies revealed that activated human intestinal immunoblasts adhere efficiently both to intestinal mucosa and synovial HEVs, • But they do not bind to peripheral lymph node vasculature, suggesting that intestinal lymphocytes have the capacity to enter the joints • Not much is known about the endothelial adhesion molecules in synovial membrane that direct homing of activated, gut derived leukocytes to joints. • Naive lymphocytes leave the blood and then adhere to mucosal HEVs by using the mucosal homing receptor integrin α4β7 and its adhesion molecule-1 (MAdCAM-1) which is expressed on HEVs in Peyer's patches and flat-walled venules in lamina propria.

28. Studies determined that gut-derived mucosal leukocytes from IBD patients are capable of binding to vessels in inflamed synovium. • They also found that small intestinal lymphocytes use multiple adhesion molecules and their corresponding endothelial ligands to adhere to synovial vessels. • In conclusion, activated intestinal lymphocytes in IBD patients • Adhere to inflamed synovial vessels using multiple adhesion molecules and their counter receptors. • These findings provide an explanation for the pathogenesis of joint inflammation in IBD patients.

29. Symptoms • Musculoskeletal manifestations in Inflammatory bowel disease (30% of pts with IBD will have one of these) • Peripheral arthritis, • Swollen tender joints, Asymmetric, > Lower limbs • Anterior chest wall pain • Dactylitis (‘sausage digit’), • Enthesitis (Achilles tendonitis & Plantarfascitis), • Arthralgia, • Sacroiliitis, • Inflammatory back pain and • <45yrs, insidious, relieved by exercise, morning stiffness, >3/12 Hx • Severity not associated with severity of IBD • Ankylosing spondylitis

30. Symptoms • Usual first presentation • Lower backache, morning stiffness, alternating buttock and chest pain. • Pain worse after sitting, standing / lying down • Arthritis symptoms is characterised by: • Recurrent brief attacks of synovitis • Asymmetric • Occurs with exacerbations in intestinal symptoms • Without progression to deformity • Self-limiting

31. Symptoms • Articular manifestations begin either concomitantly / subsequent • Spinal manifestations may precede a diagnosis of IBD • Prevalence of musculoskeletal manifestations = similar in Chron’s & UC • Symptoms usually disappear after proctocolectomy

32. Signs • Peripheral arthritis • Sudden onset pain • Erythema, hypereamia • Joint effusion • Lower limb joints mostly • Can also present with other conditions • Erythema nodosum • Anterior uveitis

33. Complication associated with IBD • Osteoporosis (cause = multifactoral) • Disease itself and associated inflammation, high-dose corticosteroid use, weight loss and malabsorption, a lack of exercise and physical activity, and an underlying genetic predisposition to bone loss.

34. Special investigation findings to support diagnosis of Spondylo-Arthropathy • There is no reliable laboratory test that can be used as a diagnostic tool in the management or diagnosis of arthropathy in IBD. • X-rays • Evidence of sacroilitis – common not obligatory • 14-20% in IBD • Bone-scan (very non-specific), CT, MRI • Can be used to detect sacroilitis • Diagnosis for peripheral arthritis = clinical • Synovial fluid – MC&S + Histology = Non-specific inflammation • Bloods • RF = Neg • HLA-B27 can be positive (50-75%) with associated ankylosingspondylitis

35. Management • There is no treatment for UC / CD • Arthropathy is mostly self-limiting • Treatment of active intestinal disease should be the • main focus. • Most IBD patients respond to: • Rest, • Physical therapy and • NSAID’s • May trigger other GIT symptoms • I wondered why the Frisbee was getting bigger, and then it hit me.

36. Drugs • NSAID’s / COX-2 inhibitors • Used to treat inflammation of arthritis • May however activate quiescent IBD, in patients where joint pain precedes onset of IBD • Sulfasalazine (Salazopyrin) • Drug of choice esp. with axial involvement • Although it seems to be more effective in peripheral arthritis patients • Pentaza • Anti-TNF-α therapy may be considered to CD patients with persistently high articular activity (axial and/or peripheral). • Steroids • Not necessary unless there are treatment failure of the above drugs – Then only short course

37. Drugs • To counteract osteopenia / osteporosis • Early Vit D & Calcium supplements • Biphosphonates, bone resorption inhibitors, bone growth promoters (in proven osteoporosis)

38. Exercise • Exercise is speculated to protect against the onset of IBD • Current research also recommend exercise to counteract some IBD-specific complications by improving: • Bone mineral density • Immunological response • Psychological health • Weight loss • Stress management ability • Some IBD patients may have limitations to the amount & intensity of exercise they may do

39. Exercise • In 1998 Ball designed guidelines specifically for IBD patients to promote exercise • Improve overall health • Strengthen muscles • Increase / maintain bone density • Guidelines include • Aerobic exercise 20-60min, 2-5x/week • Resistance training at least 2x/week

40. Specific benefits of Exercise relating to the digestive tract • Reduces RR of colon ca by 50% • Improves gastric emptying time • Improved psychological well being • Increased tolerance to pain

41. Negative exercise related effects on the GIT • Most of the negative effects on the GIT = temporary & related to • Transient decrease in gut blood flow (up to 80%) • Mechanical trauma of repeated bouncing • During prolonged, intense training or events (triathlon) 30-81% of athletes will experience • Abdominal cramps, bloating, diarrhoea (runner’s trots), heartburn, nausea, faecal incontinence, etc. • Up to 80% experience occult bleeding, can progress to ‘runners ischemic colitis’

42. Exercise and the Onset of IBD • A systemic literature review by Narula et al. found that degree of exercise via occupation neither protects against / initiates the onset of IBD

43. Exercise & Quiescent disease • In spite of multiple limiting factors in studies regarding this, there was considerable uniformity in the findings • Exercise doesn’t lead to a relapse • Also doesn’t exacerbate symptoms • Mild-moderate exercise is well tolerated by pts in remission / have mild symptoms • The same studies found IBD did significantly less exercise than the normal population • Thus higher risk for diseases of lifestyle

44. Exercise limitations of IBD patients • Brevinge et al found the % of resection in CD directly correlated to the pts exercise / working capacity • +Abnormal metabolite profile • ?Due to malnutrition due to decreased absorption area • They showed a dangerous capacity to over-exert oneself • Wiroth et all looked at muscle function and found • Reduced muscle strength & function in CD pts > in lower limbs (same as in the elderly) • This weakness was irrespective of disease state / physical fitness • Thus resistance / weight training is advised during remission periods to maintain / reverse decreased power • Remember to inform patient of limitations to avoid depression

45. Benefits of exercise in IBD • Minimize the extra-intestinal manifestations of disease • Ankylosing spondylitis (4-18% of IBD pts) • Improve strength, flexibility, decrease pain • Osteoporosis in CD pts (50% has osteopenia) • Not only related to steroid use • CD can cause stunting in paediatric skeletal growth • A randomised control trial showed significantly increased bone mineral density with CD & exercise (wasn’t long lasting when exercise was stopped)

46. Benefits of exercise in IBD • Stress management • Immune response • IBD is a chronic disease in which immune system = compromised thus and increase in immunity = useful • BMI • 20-30% of UC & CD = overweight • A 2002 study showed CD pts developed complication earlier & shorter inactive periods of disease & required more hospitalization • Patient on steroids typically gain weight, thus even more need exercise

47. Exercise prescription • Prescribing exercise to IBD depend on a multitude of variables that needs to be considered. They include: • Level of fitness • BMI • Active / inactive disease state • Current medication • Previous surgery • Disease complications thus far

48. Physical Therapy • With axial involvement • Physical therapy = important • Prevent spinal fusion – Maintain mobility • I was playing chess with my friend and he said, 'Let's make this interesting'. So we stopped playing chess.