Rheumatic diseases – classification Common rheumatic diseases

1. Rheumaticdiseases – classificationCommonrheumaticdiseases Rafał Wojciechowski, MD Senior assistant Clinical Department of Rheumatology and ConnectiveTisssueDiseases

2. Rheumatic diseases are a group of over 300 clinical units • common feature of most rheumatic diseases are chronic inflammatory process involving the connective tissue • autoimmune reactions are the cause of the inflammation

3. Division of rheumatic diseases based on American RheumatismAssociationclassification • 1. connectivetissuediseases • rheumatoidarthritis (RA) • juvenileidiopathicarthritis (JIA) • systemiclupuserythematosus (SLE) • antiphospholipidsyndrome • scleroderma • polymyositis and dermatomyositis (PM and DM) • vasculitiswithnecrosis • Sjogren'ssyndrome • overlapsyndromes • mixedconnectivetissuedisease (MCTD) • undifferentiatedconnectivetissuedisease

4. Division of rheumatic diseases based on American Rheumatism Association classification • other connective tissue diseases: • polymyalgia rheumatica • inflammation of adipose tissue • erythema nodosum • recurrent inflammation of cartilage • eosinophilic fasciitis • Still's disease in adults

5. Division of rheumatic diseases based on American Rheumatism Association classification • Spondyloarthropathies (SpA) • Ankylosing spondylitis (AS) • Reactive arthritis with Reiter syndrome • Psoriatic arthritis (PsA) • Arthritis associated with Crohn’s disease or ulcerative colitis

6. Division of rheumatic diseases based on American RheumatismAssociationclassification • Osteoarthritis (OA) • arthritis associated with infection • bacterial, viral, fungal, parasitic infection • reactive inflammation • arthritis associated with metabolic diseases and endocrine diseases • inflammation associated with the presence of crystals such as gout

7. Division of rheumatic diseases based on American RheumatismAssociationclassification • disease of bone and cartilage • Osteoporosis • Osteomalacia • hypertrophic osteoarthropathy • idiopathic generalized hyperostosis = Forestier's disease • Paget's disease

8. Division of rheumatic diseases based on American RheumatismAssociationclassification • changes in non-joint - the soft tissue rheumatism • fibromyalgiapain syndromes ( like f.ex.: neck pain, cervico-shoulder pain) • enthesopathy • bursitis • Etc.

9. Rheumatoid Arthritis (RA) • RA is a systemicinflammatorydiseasethatpredominantlymanifestsinthesynovialmembrane of joints

10. Pathophysiology of RA • The most widelyacceptedhypothesisisthediseaseistriggeredin a geneticallysusceptibleindividual by an unknownantigen. • Theinitialstagesconsist of T-cellinfilitrationintothesynovialmembrane. Theearlyinflammatoryresponseresultsinreqruitment of othercells to thesynoviumwhichisfacilitated by upregulation of adhesionmolecules and proliferation of newbloodvessels. • T-cellsactivatemacrophages to secretepro-inflammatorycytokines (TNF,IL-1, IFN). T-cellsactivateB-cells to producerheumatoidfactor. • The natural anti-inflammatory and regulatory mechanismsareoverwhelmedresultingin a runawayinflammatoryprocesssleading to thedestruction of cartilage and bone.

11. Pathophysiology of RA

12. RA - Presentation • Identifying Data: Peakincidencebetween 30-50 years old (canoccuratanyage). Prevelence of 1% in general population. Female : Male = 2.5 : 1 • Onset: Usually an insidiousonset (70%) of joint pain and swellingin an oligoarticularpatternevolving to a polyarthritis. Occasionallycansee a subacutepresentation (20%), an acutepresentation (10%), or a precedingpalindromicpresentation. Morningstiffness > 60 minutes, gellingphenomenon, decreased energy and poorsleep, weightgain, rareappetiteloss and weightlosswhensevere

13. RA - Presentation • Progression: as thediseaseprogressesmorejointsbecomecontinouslyinvolvedleading to thesymmetricalpolyarthritis. Withcontinuedinflammationdamage to jointsmayresultwiththeinitialfindings of erosions of plainradiographs. Almost 90% jointsultimatelyaffectedin a givenpatientareinvolvedduringthe first year of disease. By 4 months of symptoms, 50% of patients will haveerosions on MRI. By 3 years, 70-90% of patientsdemonstrateerosions on X-ray. • ConstitutionalFeatures: malaise, anorexia and weightloss • Functional Status: reducedfunctional status and difficultieswithactivities of dailyliving, loss of employment

15. 1987 Criteria for the Classification of Acute Arthritis of Rheumatoid Arthritis • 1. Morning stiffness Morning stiffness in and around the joints, lasting at least 1 hour before maximal improvement • 2. Arthritis of 3 or more joint areas At least 3 joint areas simultaneously have had soft tissue swelling or fluid (not bony overgrowth alone) observed by a physician. The 14 possible areas are right or left PIP, MCP, wrist, elbow, knee, ankle, and MTP joints • 3. Arthritis of hand joints At least 1 area swollen (as defined above) in a wrist, MCP, or PIP joint • 4. Symmetric arthritis Simultaneous involvement of the same joint areas (as defined in 2) on both sides fo the body (bilateral involvement of PIPs, MCPs, or MTPs is acceptable without absolute symmetry) • 5. Rheumatoid nodules Subcutaneous nodules, over bony prominences, or extensor surfaces, or in juxtaarticular regions, observed by a physician • 6. Serum rheumatoid factor Demonstration of abnormal amounts of serum rheumatoid factor by any method for which the result has been positive in <5% of normal control subjects • 7. Radiographic changes Radiographic changes typical of rheumatoid arthritis on posteroanterior hand and wrist radiographs, which must include erosions or unequivocal bony decalcification localized in or most marked adjacent to the involved joints (osteoarthritis changes alone do not qualify) * For classification purposes, a patient shall be said to have rheumatoid arthritis if he/she has satisfied at least 4 or these 7 criteria. Criteria 1 through 4 must have been present for at least 6 weeks. Patients with 2 clinical diagnoses are not excluded. Designation as classic, definite, or probable rheumatoid arthritis is not to be made.

16. Hands with joint swelling and damage fromrheumatoid arthritis

17. The 2010 ACR-EULAR classification criteria for rheumatoid arthritis Target population (Who should be tested?): Patients who have at least 1 joint withdefinite clinical synovitis (swelling)with the synovitis not better explained by another disease Classification criteria for RA (score-based algorithm: add score of categories A–D; a score of ≥6/10 is needed for classification of a patient as having definite RA) A. Joint involvement • 1 large joint - 0points • 2-10 large joints – 1 point • 1-3 small joints (with or without involvement of large joints) - 2points • 4-10 small joints (with or without involvement of large joints) – 3points • >10 joints (at least 1 small joint) - 5points B. Serology (at least 1 test result is needed for classification) • Negative RF and negative ACPA – 0points • Low-positive RF or low-positive ACPA – 2points • High-positive RF or high-positive ACPA – 3points C. Acute-phase reactants (at least 1 test result is needed for classification) • Normal CRP and normal ESR – 0points • Abnormal CRP or abnormal ESR – 1 point D. Duration of symptoms • <6 weeks – 0points • ≥6 weeks – 1 point

18. The 2010 Tree Algorithm for classifying definite RA (green circles) or for excluding its presence (red circles) among those who are eligible to be assessed by the 2010 ACR-EULAR RA Classification Criteria

19. RA – physical examination • Vitals – usuallynormal; • Cutaneous: palmarerythrema, Rheumatoidnodules on extensorsurfaces of thehands, forearms, periungalinfarctsifassoc. withRheumatoidvasculitis (severedisease) • Hand & Neck: ocularinvolvementwithscleritis, episcleritis and conjunctivitis; siccafeatures; C-spineinstability • Respiratorty: cracklessecondary to interstitialfibrosis; diminishedbreathsound and dullness on percussiondue to pleuraleffusion; pleuralfrictionrubSeveredisease) • Cardiovascular: pericardialfrictionrub; heartsmurmurs (severedisease)

20. RA – physical examination • Musculoskeletal: PIPs (proximalinterphalangealjoints)– fusiformswelling, pain, tenderness to palpate, flexiondeformities, swan-neckdeformities, boutonnieredeformities, ligamentousinstability, rheumatoidnodules; MCPs (metacarpophalangealjoints)– swelling, pain, tenderness to palpate, flexiondeformities, ulnardrift and subluxation; Thumbs – Z deformity; Wrists – dorsalswelling, pain, tenderness, radialdeviation, volarsubluxationcarpaltunnelsyndrome and interosseouswasting; flexortendonthickeningwithnodules

21. RA – physical examination • Musculoskeletal: Elbow and shoulderinvolvement; Knee and Hipinvolvement; Foot – hindfootvalgusdeformity and forefootabduction (pronated); MTP – inflammationwithlossvisibility of theextensortendons and splayedtoesliftedofftheground. Subluxation of MTPswithdistalmigration of thefat pad and callousformation • Neurologic: neuropathy – polyneuropathyormononeuritismultiplex; upper motor neuron signswithcervicalspineinvolvementcausingspinalcordcompromise

24. RA - Investigations • CBS: anaemia of chronicinflammationorsecondary to bloodloss (NSAIDs) or to bonemarrowsupression; leukopenia withFelt’sorsecondary to medications; thromocytosiswithinflammationorthromobocytopeniasecondary to Felty’sormedications • ESR/CRP: usuallyelevatedhoweverrarelymay be normal • RF: earlydisease (30-50%); establisheddisease (70-85%); • Anti-CCP: higlyspecific for RA (95%) but poorsensitivity • ANA: presentin 25% patients

25. RA - Investigations • PlainRadiographs: • Bones: periarticular osteopenia, periarticularcystsifrheumatoidrobustus; • Joints: uniform joint spacenarrowing and marginalerosions; erliesterosionsin 2’nd and 3’rd metacarpalheads, ulnearstyloid, medialaspect of first metacarpalhead • Alignment: demage to jointsresultsinmelalignment: PIPs – contractures, swan-neckdeformities, boutonnieredeformities; MCPs: subluxation and ulnardeviation; Thumbs: Z deformity; Wrists: radialdeviation and volarsubluxation; C-Spine: A-A instability (vertiacal, horizontal and lateral); MTPs: subluxation, angulationdeformities; • Soft Tissue: periarticularswelling and evidence of joint effusions;

26. RA - prior to treatment • There are 4 issues to consider: 1/ Baseline disease activity and demage (data form Patiens History and physical examination, lab findings( ESR/CRP, RF and anti-CCP presence, HAQ, VAS, Radiographic assesments, etc) 2/ Prognostic factors ( extra-articular features, presence of RF/anti-CCP, rheumatoid nodules, other co-morbidities: liver and renal function, etc) 3/ Treatments (if any) have been in the past 4/ Contra-indications to medications

27. Diseaseactivityclassification – DAS 28 • Swollen and Tender joint count (28 joints) • ESR / CRP • VAS – patient’sdiseaseacivityassesment (0-100mm) • REMISSION : DAS28< 2.6 • LOW ACTIVITY: DAS28=2.6-3.2 • MODERATE ACIVITY: DAS28=3.2-5.1 • SEVERE ACTIVITY: DAS28>5.1

29. RA - treatment • DMARDsaremainstay of RA therapydue to theireffect on inflammation, function, and prevention of long-term disability. • Initiate DMARD therapyearly (within 2 monthsifavailable) as treatmentwithDMARD’s, eithermonotherapyorcombinationtherapy, produces superior long-term outcomes. • Methotrexateaccelerated to doses of 25mg/weekwithin 6-8 weeks, isthecurrent „gold standard” therapy. • Leflunomide, Sulfasalazine, and orcombinationtherapiesareotheracceptablealternatives.

30. RA - treatment • Corticosteroids (CS): low dose (5-10mg of predniosone) are higly effective in controling symptoms in patients with active RA • CS may slow the rate of joint damage and thereforemay have a disease modifying effect • The benefits of low dose of CS should always be balanced against the risks • CS can be used nicely as bridge therapy while waiting for a DMARD to work.

31. RA - treatment • NSAIDs and COXIBs: haveanalgesic and anti-inflammatoryproperties but do not alterthecourse of thediseaseorprevent joint destruction and shouldn’t be usedalone for thetreatment of RA • Biologics: the high cost of treatmentmay limit theiruse as first linetherapyin RA. Thecurrentapproachis to usebiologicsifthereisinadequateresponseorintolerance of traditional DMARD therapy. Infliximab, etanercept, adalimumab, golimumabortocilizumab and rituximabarehighlyeffectiveinearly RA and/orthosewithactive RA whohavefailedprevious DMARD therapy.

32. RA - prognosis • Two general categories: 1) 5-20% have intermittent disease with periods of exacerbation and a relatively good prognosis; 2) 80-85% have progressive disease with either a slow or rapid course: 50% of patients will be functional class 3 or 4 within 10 years; 30% of patients will be unemployed at 5 years; • Higher incidence of infections, cardiovascular disease and lymphoma.

34. Spondyloarthropathies • The term ‘spondyloarthritis’ (SpA) comprises AS, reactive arthritis, arthritis/spondylitis associated with psoriasis, and arthritis/spondylitis associated with inflammatory bowel disease (IBD). • There is considerable overlap between the single subsets. • The main link between each is the association with the human leukocyte antigen(HLA)-B27, the same pattern of peripheral joint involvement with an asymmetrical,often pauciarticular, arthritis, predominantly of the lower limbs, and the possibleoccurrence of sacroiliitis, spondylitis,enthesitis,dactylitis and uveitis. • All SpAsubsetscan evolve into AS, especially in those patients who are positive for HLA-B27. The SpAsubsets can also be split into patients with predominantly axial and predominantly peripheral SpA with an overlap between the two parts in about 20–40%of cases.

35. Spondyloarthropathies • Spondyloarthropathies (SpA) • Ankylosing spondylitis • Reactive arthritis with Reiter syndrome • Psoriatic arthritis • Arthritis associated with Crohn’s disease or ulcerative colitis

36. Epidemiology of ankylosingspondylitis • AS is a disease that starts normally in the third decade of life, withabout 80% of patients developing the first symptoms before the ageof 30 and less than 5% of patients being older than 45 at the start of the disease. • Upto 20% of patients are even younger than 20 years when they experience theirfirst symptoms. • Patients who are positive for HLA-B27 are about10 years younger than HLA-B27-negative patients when the disease starts.

37. Epidemiology of ankylosingspondylitis • Men are slightly more affected than are women, with a ratio of about 2:1. • There is a clear correlation between the prevalence of HLA-B27 and theprevalence of AS in a given population: the higher the HLA-B27 prevalence thehigher the AS prevalence. • HLA-B27 is positive in 90–95% of AS patients and in about 80–90% of patients with non-radiographic axial SpA. • This percentage goes down to about60% in AS patients who also have psoriasis or IBD. • In predominant peripheralSpA, less than 50% of patients are positive for HLA-B27

38. Clinical manifestations of ankylosingspondylitis Inflammatory back pain • The main clinical symptoms in AS are pain and stiffness of the back, pre-dominantly of the lower back and the pelvis, but any part of the spine can beinvolved. • Typical for AS/spondyloarthritis (SpA) is inflammatory back pain(IBP) which is defined clinically and not by laboratory tests such as CRP or ESR. • Patients complainabout morning stiffness of the back, with improvement on exercise but not by rest. In addition, or alternatively, they report awakening at night, mostly in thesecond half of the night, because of back pain which improves on getting upand moving around. • Furthermore, back pain should be chronic(>3 months duration) not acute, and it should occur for the first time beforethe age of 45 years, because the disease starts at a young age; this also helpsto differentiate it from degenerative spine disease, the prevalence of whichincreases with age. Most patients report a mixture of pain and stiffness in thespine, although either can be the main or only symptom.

39. Clinical manifestations of ankylosingspondylitis Restriction of spinal mobility  • Further in the course of the disease, syndesmophytes and ossification of the facet joints can develop, resulting in restriction of spinal mobility.The long-term outcome is strongly determined by restriction of spinalmobility. However, not all AS patients have syndesmophytes. • In AS patientswith a disease (symptom) duration of less than 10 years syndesmophytesare detectable in only about 25%, and in patients with a mean diseaseduration of more than 20 years syndesmophytes are visible on radiographsin about 60%. • In addition to restriction of spinal mobility patients can developflexion contractures of hip and knee joints, which together result in a characteristic posture for advanced disease in AS patients.

41. SYNDESMOPHYTES aregenerallyseenonlyintheseronegativespondyloarthropathies (eg.AnkylosingSpondylitis)Thesearedue to inflammation and ossification of theouterfibers of theannulusfibrosus, known as theSharpey'sfibers(In AnkylosingSpondylitis)

43. Modified Schober test to assess motion of the lumbar spine (a) the patient standserect and the clinician marks an imaginary line connecting both posterior superior iliac spines (b) another mark is placed 10 cm above; (c) the patient bendsforward maximally, and the difference is measured. The best of two attempts is recorded andthe increase in centimetres is recorded to the nearest 0.1cm

44. Measuring cervical and thoracic spine extension: occiput-to-wall and tragus-to-wall distance. The heels and back rest against the wall, with the chin at usual carryinglevel. The patient tries to touch the head against the wall. The best of two tries is recordedin centimetres (eg, 10.2cm). The occiputtowall (black arrow) or tragustowall (whitearrow) distance can be measured

45. Measuring cervical rotation to assess neck mobility in patients with AS • (a) • the patient sits straight on a chair, chin level, hands onthe knees. The assessor places a goniometer at the top of the head in line with the nose; • (b) • the assessor asks the patient to rotate the neck maximally to the left, follows withthe goniometer, and records the angle between the sagital plane and the new planeafter rotation. A second reading is taken and the best of the two is recorded for the leftside. The procedure is repeated for the right side. The mean of left and right is recordedin degrees (0-90°) • (normal>70°)

46. Chest expansion The patient rests his/herhands on or behind the head. The chestis measured at the fourth intercostal level anteriorly. (a)the maximal inspiration is recorded; (b)the maximal expiration is recorded. The difference is recorded in centimetres (eg, 4.3cm)and the best of two tries is noted.

47. Extraspinalrheumaticmanifestations Peripheral arthritisoccurs frequently, but often transiently, in AS and presentstypically as an asymmetrical arthritis and/or as an arthritis predominantly of the lower limbs. Enthesitis (inflammation at the insertion of tendons, ligaments or capsules intobone) is also a frequent manifestation in AS. • The lower limbs are most frequently affected. • The sites affected by inflammation in peripheral joints can be both thesynovium and the insertion of tendons/ligaments at bone.However, inflammation is possible at any enthesial site

48. Modified New York classificationcriteria for ankylosingspondylitis • Clinicalcomponents • 1 Low back pain and stiffness for >= 3 monthsthatimproveswithexercise but not withrest • 2 Limitation of lumbarspinemobilityinboththesagittal (sideways) and frontal (forward and backward) planes • 3 Limitationinchestexpansion as comparedwithnormalrange for age and gender • Radiologiccomponent • Unilateralsacroilitis of grade 3 or 4 orbilateralsacroilitis of grade >= 2 • Diagnosis: • Definite AS iftheradiologicalcriterionis associated withatleast one clinicalcomponent • Probable AS if: a/ onlythethreeclinicalcomponentsarepresent b/ onlyradiologiccomponentispresent

49. AS - management • General: education • Physiotherapy: regularexercisemay slow theprogression of spinalstiffness and restriction – itisimperativethatpatientsworkwith a physiotherapist and understandthe role of streching and exercise to minimizethe long-term impact of theircondition

50. NSAIDs & Analgesics: maydramaticallyreducepain and spinalstiffness; long-actingNSAIDstakenatnightmayreducenightdiscomfort and morningstiffness • Corticosteroids: as localinjectionsmay be a value for enthesealpain and peripheralsynovitis; injectionsintosacroiliacjointsmay be benefit; onlybriefcourses of oralorparenteral CS may be helpfulinovercomingseverespinalorperipheralinflammatorydisease. • DMARDs: Sulfasalazineisusefulinperipheralsynovitis but not as effectiveinspinalinvolvemnet; Methotrexate? • Biologics: onlyTNF-inhibitorshavedocumented a significant and sustainedreductioninthesigns and symptoms of AS. Theyshould be given to patientswithperisiten high diseaseactivitydespiteconventionaltherapy. • Bisphosphonates: improveosteoporosis associated with AS.