Rheumatoid ArthritisDr Pratap Sagar Tiwari

Case scenario: summary

15 yrs old ,m presented with multiple joints pain esp

knees, ankle, elbow and wrists. Migratory in nature.

O/E minimal signs of inflammation.

Xray was unremarkable.Synovial fluid analysis:

sterilePain relieved with NSAIDS

35 y female presented with symmetrical polyarthritis

including small joints of the hands and wrists but excluding

the DIP. Morning stiffness > 1 hr.Elevated acute phase reactants

with positive RFs.X ray shows erosions and bony

decalcifications. Along with systemic

features ,extraarticular manifestations were also

present.

55 y old female presented with pain in the knee joints with morning

stiffness but <30 min. Increased pain during

evening. O/E involved joints were hard and bony without inflammatory changes.

Crepitus was heard. Exam findings were limited to joints only.

A CB

INTRODUCTION: Rheumatoid Arthritis• RA is a chronic, systemic, inflammatory disorder of unknown etiology

that primarily involves joints with characteristics features of persistent inflammatory synovitis usually involving peripheral joints in a symmetrical distribution.

Prevalence• RA affects about 1% of the world's population1 when defined by either the presence of

serum RF or erosive changes on radiographs in pt with a compatible clinical presentation. • Its incidence is two to 3 X greater in W, and this disparity is most pronounced in patients

younger than 50 years.2

• The incidence of RA continues to increase with age until about the 7th decade of life.3

• Cigarette smoking ↑ the risk of developing RA & negatively influences disease course.4

• Genetic susceptibility , the association of HLA-DR with RA is well established. There is an increased relative risk of RA of about 4 to 5 in patients with this allele.5

1. Firestein GS. Etiology and pathogenesis of rheumatoid arthritis. In: Ruddy S, Harris E, Sledge C (eds): Kelly's Textbook of Rheumatology. 6th ed. Philadelphia: WB Saunders, 2001, 921-966.

2. Linos A, Worthington JW, O’Fallon WM, Kurland LT. The epidemiology of rheumatoid arthritis in Rochester, Minnesota: A study of incidence, prevalence, and mortality. Am J Epidemiol. 1980, 111: 87-98.

3. Silman AJ, Hockberg MC. Epidemiology of the Rheumatic Diseases. Oxford: Oxford University Press, 1993.

4. Stolt P, Bengtsson C, Nordmark B, et al: Quantification of the influence of cigarette smoking on rheumatoid arthritis: Results from a population based case-control study, using incident cases. Ann Rheum Dis. 2003, 62: 835-841.

5. Stastny P. Association of the B-cell alloantigen DRw4 with rheumatoid arthritis. N Engl J Med. 1978, 298: 869-871.

Pathophysiology

Note: the explaination of pathogenesis is beyond the scope of this slide

Rheumatoid Arthritis Criteria (1987 revision, American Rheumatism Association)1. Morning stiffness (in/around joints, >1 hr before maximal improvement)2. Arthritis (swelling) of 3 or more joint areas (observed by physician)3. Symmetric arthritis (swelling, NOT bony overgrowth)4. Arthritis of Hand joints (wrists, MCPs or PIPs)5. Rheumatoid nodules6. Rheumatoid factor (serum)7. Radiographic changes (erosions and/or peri-articular osteopenia in hand/wrist

joints)Requirements: ≥4 of the above 7 criteria. Criteria 1-4 must have been present for at least 6 weeksReference: Arnett et al. The American Rheumatism Association1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum 1988;31:315-324

This criteria demostrated 91-94% sensitivity and 89 % specificity for RA when compared with non RA rheumatic disease control subjects.

Deformities: pictures'swan neck' deformity boutonnière or 'button hole' deformity

Source: wikipedia A=User:Phoenix119 B=author:Prashanthns [cited sep 29 2015]DIP hyperflexion with PIP hyperextension PIP flexion with DIP hyperextension

Deformities: picturesZ deformity of the thumb 'cock-up' toe deformities

source: http://www.londonpodiatry.com/podiatry/conditions/toe-problemsSource; http://handarthritis.com/handarthritisdeformities.shtmldorsal subluxation of the MTP joints

The 2010 American College of Rheumatology/European League Against Rheumatism classification criteria for rheumatoid arthritis

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)

Aletaha et al. 2010 Rheumatoid arthritis classification criteria: an American College of Rheumatology / European League Against Rheumatism collaborative initiative. Ann Rheum Dis 2010;69:1580-1588.

Palindromic rheumatism• The onset of RA is episodic in a few patients, with one to several joint areas being

affected sequentially for hrs to days, with symptom free periods that may last from days to mnths; an episodic pattern referred to as "palindromic rheumatism."

• The proportion of pts presenting with PR who progress to develop RA or another well defined disease varies between studies. In one study of 60 pts with PR followed over 20 yrs, 40 (67 %) developed RA [1]. In another study, among 147 such patients, 41 were eventually diagnosed with RA (28 percent) and 4 with other disorders (3 with SLE and 1 with Behçet’s disease) [2].

• In one study, a majority of those with PR also had ACPA, a serologic finding that is common in RA [3 ]. In another study, ACPA were positive in 83 % of pts who progressed to definite RA [ 4].

1. Koskinen E, Hannonen P, Sokka T. Palindromic rheumatism: longterm outcomes of 60 patients diagnosed in 1967-84. J Rheumatol 2009; 36:1873.

2. Maksymowych WP, Suarez-Almazor ME, Buenviaje H, et al. HLA and cytokine gene polymorphisms in relation to occurrence of palindromic rheumatism and its progression to rheumatoid arthritis. J Rheumatol 2002; 29:2319.

3. Salvador G, Gomez A, Vinas O, et al. Prevalence and clinical significance of anti-cyclic citrullinated peptide and antikeratin antibodies in palindromic rheumatism. An abortive form of rheumatoid arthritis? Rheumatology (Oxford) 2003; 42:972.

4. Russell AS, Devani A, Maksymowych WP. The role of anti-cyclic citrullinated peptide antibodies in predicting progression of palindromic rheumatism to rheumatoid arthritis. J Rheumatol 2006; 33:1240.

Extra-articular manifestations of R diseaseSystemic MusculoskeletalFeverWeight loss Fatigue

Muscle-wastingTenosynovitis /BursitisOsteoporosis

Hematological Ocular AnaemiaThrombocytosis Eosinophilia

Episcleritis /Scleritis ScleromalaciaKeratoconjunctivitis sicca

Vasculitis Cardiac (30 % in +RA)Digital arteritisUlcersPyoderma gangrenosum

Pericarditis/Myocarditis/Endocarditis Conduction defectsCoronary vasculitis/Granulomatous aortitis

Extra-articular manifestations of R diseasePulmonary Neurological

NodulesPleural effusionsFibrosing alveolitis BronchiolitisCaplan's syndrome

Cervical cord compressionCompression neuropathies Peripheral neuropathyMononeuritis multiplex

Amyloidosis

Caplan's syndrome (or Caplan disease or Rheumatoid pneumoconiosis is a combination of rheumatoid arthritis (RA) and pneumoconiosis that manifests as intrapulmonary nodules, which appear homogenous and well-defined on chest X-ray.

Causes of anemia in RA• Anemia of chronic disease• Megaloblastic anemia due to folate deficiency or associated

pernicious anemia• Felty’s syndrome• Drugs: NSAID causing iron deficiency , Gold causing bone marrow

suppression

Felty's syndromeRisk factorAge of onset 50-70 yrsFemale > maleLong-standing RA Deforming but inactive diseaseSeropositive for RF

Felty's syndrome is characterized by the

combination of rheumatoid arthritis, splenomegaly and

neutropenia.

Disease associations of rheumatoid factor [1,2]Rheumatoid arthritis (60-70%).Sjögren's syndrome (85-95%).Felty's syndrome (>95%).Systemic sclerosis (~30%).Infective endocarditis.Systemic lupus erythematous (~25-35%).Infectious mononucleosis.Hepatitis.Juvenile rheumatoid arthritis.

Tuberculosis.Dermatomyositis.Syphilis.HIV.Influenza.Malignancy.Sarcoidosis.Leukaemia.Healthy individuals 5% increasing to 20% over the age of 65 yrs.

Ref:1. Wilson D; Rheumatoid factors in patients with rheumatoid arthritis. Can Fam Physician. 2006 Feb;52:180-1.2. Longmore M, Wilkinson IB and Rajagopalan SR; Oxford Handbook of Clinical Medicine, 6th ed, 20043. Nishimura K, Sugiyama D, Kogata Y, et al; Meta-analysis: diagnostic accuracy of anti-cyclic citrullinated peptide antibody and rheumatoid factor for rheumatoid arthritis. Ann Intern Med. 2007 Jun 5;146(11):797-808.

RA- sensitivity in established disease is only 60-70% with a specificity of 78%.[3] The higher the level in rheumatoid disease the worse the joint destruction and the greater the chance of systemic involvement.

Presence of RA factor is not specific for RA and its presence doesn’t

establish diagnosis of RA but is of prognostic significance as patients with high titres tend to have more severe & progressive disease with

extraarticular manifestations.

Seronegative spondyloarthropathies: conditions a/w HLA-B27• Ankylosing spondylitis• Reactive arthritis (reiter’s syndrome)• Psoriatic arthritis• Enterpathic Arthritis (Arthropathy of IBD )• Undifferentiated spondyloarthopathies

Notes: pattern of small joint involvementOsteoarthritis Rheumatoid arthritis Psoriatic arthritis

Involvement of PIP, DIP & 1st carpometacarpal joint (base of the thumb)

Involvement of any small joints of the hand ie PIP, MCP, wrist

Involvement of DIP, PIP, MCP, and wrist

Sparing of MCP & wrist Sparing of DIP NA

• DIP is the mc form of idiopathic OA• Heberden’s nodes or bony enlargement of DIP joints are the mc form of idiopathic OA.• Bouchard’s nodes: bony enlargement of PIP joint in OA.• Heberden’s nodes: Bony enlargement of DIP joint in OA.

Rheumatic arthritis• The natural history of arthritis due to RF consists of inflammation affecting several joints in

quick succession, each lasting for a few days to a week . • The knees, ankles, elbows, and wrists are affected most commonly; the leg joints are

typically involved first. • The onset of arthritis in different joints usually overlaps, giving the appearance that the

disease "migrates" from joint to joint. Thus, the terms "migrating" or "migratory" are used .• Joint pain usually is more prominent than objective signs of inflammation & is almost

always transient. • Radiography of an affected joint may demonstrate a slight effusion but is usually

unremarkable.• The natural history of the polyarthritis in ARF is altered by empiric treatment with NSAIDS.• Analysis of the synovial fluid in RF with arthritis generally demonstrates sterile.

Osteoarthritis• Deep, achy joint (typically weight bearing large joints)pain exacerbated by extensive use - The disease’s

primary symptom• Reduced range of motion and crepitus - Frequently present• Stiffness during rest (gelling) - May develop, with morning joint stiffness usually lasting for <30 minutesOsteoarthritis of the hand• DIP joints are most often affected• PIP joints and the joints at the base of the thumb are also typically involved• Heberden nodes, which represent palpable osteophytes in the DIP joints, are more characteristic in women

than in men• Inflammatory changes are typically absent, less pronounced, or go unnoticed. (Hard bony swelling)Arthrocentesis :The presence of noninflammatory joint fluid helps distinguish OA from other causes of joint pain. Other synovial fluid findings that aid in the differentiation of OA from other conditions are negative Gram stains and cultures, as well as the absence of crystals when fluid is viewed under a polarized microscope.Physical examination findings: mostly limited to affected joints

Rheumatoid Arthritis• The typical picture of BL symmetrical inflammatory polyarthritis involving

small and large joints in both upper & lower extrimities with sparing of axial skeleton except the cervical spine suggests the diagnosis. harrison

• Characterize by erosive arthritis.• DIP joints are typically spared. harrison

• Extraarticular manifestations are seen in upto 40 % of patients. harrison

• Rheumatoid nodules are seen in 20 % . harrison

• Most strongly a/w class II MHC allele HLA DR4.• Anti CCP antibodies are the most specific blood test (95%)..CMDT

Other DD• Infectious arthropathies • systemic lupus erythematosus • Polymyositis and dermatomyositis • crystal arthropathies • Polymyalgia rheumatica and giant cell arteritis • Fibromyalgia • Sarcoidosis

End of slides• Next: Management of Rheumatoid Arthritis

References:• Davidson’s

• Harrison 18th ed

• Uptodate 20.3

• Medscape

• RA guidelines