Rheumatoid arthritis is an autoimmune disease where the immune system attacks the body's own tissues, commonly affecting the joints. It is characterized by synovial inflammation, autoantibody production, cartilage and bone destruction, and systemic effects. Genetics, environment, and chance play a role in its pathogenesis. Symptoms are treated with medications like DMARDs and biologics to reduce inflammation and slow joint damage. Investigations include labs, imaging, and diagnostic criteria. Long term complications involve deformities, contractures, and systemic impacts if untreated. Surgical options are considered if conservative treatment fails or late stage deformities develop.

1. AUTOIMMUNE DISEASE
(RHEUMATOID ARTHRITIS)
Presenter: Dr Laichena
Moderator: Dr King’ori

2. Autoimmune disorders occur when the body's immune system
inappropriately attacks the body's own health tissues and may be
restricted to specific organs or involve a particular tissue ion different
parts of the body
National institute of Arthritis and Musculoskletal and Skin diseases. Autoimmune Diseases

3. Outline
Definition of autoimmune diseases
Rheumatoid arthritis
History
Pathogenesis of RA
Investigations
Diagnosis criteria
Treatment
Specific orthopaedic manifestations in RA

4. Common Autoimmune diseases in
Orthopaedics
• Rheumatoid arthritis
• Seronegative spondyloarthropathies:
Ankylosing spondylitis
Reiters syndrome and reactive arthritis
Psoriatic arthritis
Enteropathic arthritis
• Juvenile idiopathic arthritis
• Connective tissue diseases

5. Rheumatoid Arthritis
History
• Arthritis and diseases of the joints have been plaguing mankind since
ancient times.
• In around 1500 BC the Ebers Papyrus described a condition that is
similar to rheumatoid arthritis.
• Hippocrates described arthritis in general in 400 BC.
• A B Garrod in 1858 named the disease rheumatoid arthritis replacing
the old terms arthritis deformans and rheumatic gout

6. History of treatment of rheumatoid arthritis
• In the olden days treatments included bloodletting and leeching.
• In the Far East developed practices of acupuncture, acupressure,
moxibustion (use of heat), cupping were used
• Gold, bismuth, arsenic and copper salts were used with varying rates
of success.
• Gold however has shown success over years of use and is still a part
of DMARDs

7. Disease Modifying Anti-rheumatic drugs (DMARDs)
• Payne in 1895 was the first to suggest the use of quinine
• In 1957 Baguall used chloroquine and now hydroxychloroquine is still
part of the DMARDs
• In 1940’s sulphasalazine was developed as an anti-inflammatory and
still forms part of DMARDs.
• It was not until 1980’s that the role of methotrexate in rheumatoid
arthritis was discovered

8. Anti-TNF antibodies
In 1993 Anti-TNF antibodies were shown to be effective in the
treatment of patients with rheumatoid arthritis.
Historical Perspective on the Etiology of Rheumatoid Arthritis Pouya Entezami, BS, David A. Fox, MD, Philip J. Clapham, BS, and Kevin
C. Chung, MD, MS

9. PATHOGENESIS OF RA
• Rheumatoid arthritis is characterized by synovial inflammation and
hyperplasia, autoantibody production, cartilage and bone
destruction, and systemic features, including cardiovascular,
pulmonary, psychological, and skeletal disorders
• involves a complex interplay among genotype, environmental
triggers, and chance

11. The long-established association with the HLA–DRB1 locus has been
confirmed in patients who are positive for rheumatoid factor or ACPA;
alleles that contain a common amino acid motif (QKRAA) in the HLA-DRB1
region, termed the shared epitope, confer particular susceptibility.
MacGregor AJ, Snieder H, Rigby AS, et al. Characterizing the quantitative genetic contribution to rheumatoid arthritis using data
from twins. Arthritis Rheum 2000;43:30-7.
Wellcome Trust Case Control Consortium. Genome-wide association study of 14,000 cases of seven common diseases and 3,000
shared controls. Nature 2007; 447:661-78

12. • Smoking and other forms of bronchial stress e.g., exposure to silica
increase the risk of rheumatoid arthritis among persons with
susceptibility HLA– DR4 alleles.
• smoking and HLA-DRB1 alleles synergistically increase one’s risk of
having ACPA
• The formation of immune complexes during infection may trigger the
induction of rheumatoid factor, a high-affinity autoantibody against
the Fc portion of immunoglobulin

13. The gastrointestinal microbiome is now recognized to influence the
development of autoimmunity in articular models, and specific clinical
bacterial signatures that are associated with autoantibody positive
rheumatoid arthritis are emerging
Scher JU, Ubeda C, Pillinger MH, et al. Characteristic oral and intestinal microbiotain rheumatoid arthritis (RA): a trigger for
autoimmunity? Arthritis Rheum 2010;62:Suppl:1390. abstract.

16. Synovial Immunologic Processes and Inflammation
• Synovitis occurs when leukocytes infiltrate the synovial compartment.
• Leukocyte accumulation primarily reflects migration rather than local
proliferation.
• Cell migration is enabled by endothelial activation in synovial
microvessels, which increases the expression of adhesion molecules
and chemokines.
.
Szekanecz Z, Pakozdi A, Szentpetery A, Besenyei T, Koch AE. Chemokines and angiogenesis in rheumatoid arthritis.
Front Biosci (Elite Ed) 2009;1:44-51.
Polzer K, Baeten D, Soleiman A, et al.Tumour necrosis factor blockade increases lymphangiogenesis in murine and
human arthritic joints. Ann Rheum Dis 2008;67:1610-6.

17. Accordingly, neoangiogenesis, which is induced by local hypoxic
conditions and cytokines, and insufficient lymphangiogenesis, which
limits cellular egress, are characteristic features of early and
established synovitis
These microenvironmental changes, combined with profound synovial
architectural reorganization and local fibroblast activation, permit the
buildup of synovial inflammatory tissue in rheumatoid arthritis

19. Cartilage Damage
• A hyperplastic synovium is the major contributor to cartilage damage.
• Loss of the normally protective effects of synovium alter the protein-
binding characteristics of the cartilage surface, promoting FLS
adhesion and invasion.
• FLS synthesis of MMPs promotes disassembly of the type II collagen
network, a process that alters glycosaminoglycan content and water
retention and leads directly to biomechanical dysfunction.

20. • MMP-14 appears to be the predominant MMP expressed by FLSs to
degrade the collagenous cartilage matrix.
• Other matrix enzymes (e.g., ADAMTS 5) degrade aggrecan and thus
further diminish cartilage integrity.
• Endogenous enzyme inhibitors, such as TIMPs, fail to reverse this
destructive cascade.

21. • Chondrocytes physiologically regulate matrix formation and cleavage:
under the influence of synovial cytokines and reactive nitrogen
intermediates, cartilage is progressively deprived of chondrocytes,
which undergo apoptosis.
• These processes ultimately lead to the destruction of the surface
cartilage and the radiographic appearance of joint-space narrowing.

22. Bone destruction
• Bone Erosion Bone erosion occurs rapidly and is associated with
prolonged, increased inflammation.
• Synovial cytokines, particularly macrophage colony-stimulating factor
and receptor activator of NF-κB ligand (RANKL), promote osteoclast
differentiation and invasion of the periosteal surface adjacent to
articular cartilage.
Visser H, le Cessie S, Vos K, Breedveld FC, Hazes JM. How to diagnose rheumatoid arthritis early: a prediction model
for persistent (erosive) arthritis. Arthritis Rheum 2002;46:357-65

23. • TNF-α and interleukin-1, 6, and potentially 17 amplify osteoclast
differentiation and activation.
• Moreover, clinical inhibition of TNF-α, interleukin-6, and RANKL retards
erosion in rheumatoid arthritis. Notably, blockade of RANKL acts only on
bone, with no effect on inflammation or cartilage degradation.
• Osteoclasts have the acidic enzymatic machinery necessary to destroy
mineralized tissues, including mineralized cartilage and subchondral bone;
destruction of these tissues leads to deep resorption pits, which are filled
by inflammatory tissue.
• Schett G, Teitelbaum SL. Osteoclasts and arthritis. J Bone Miner Res 2009;24:1142-6.
• Schett G, Stach C, Zwerina J, Voll R, Manger B. How antirheumatic drugs protect joints from damage in rheumatoid
arthritis. Arthritis Rheum 2008;58:2936-48.

24. • Mechanical factors predispose particular sites to erosion.
• Breach of cortical bone permits synovial access to the bone marrow,
which causes inflammation of the bone
• Eroded periarticular bone shows little evidence of repair in
rheumatoid arthritis, unlike bone in other inflammatory
arthropathies.
• Jimenez-Boj E, Redlich K, Turk B, et al. Interaction between synovial inflammatory tissue and bone marrow in rheumatoid
arthritis. J Immunol 2005;175: 2579-88.

25. Systemic long term complications in RA

26. Investigations -LAB
• Routine viral screening by serologic testing does not significantly
facilitate the diagnosis of RA in patients with early RA, nor is it helpful
as a potential identifier of disease progression.
• Potentially useful laboratory studies in suspected RA fall into 3
categories—markers of inflammation, hematologic parameters, and
immunologic parameters

30. IMAGING
• Radiography remains the first choice for imaging in RA; it is
inexpensive, readily available, and easily reproducible, and it allows
easy serial comparison for assessment of disease progression
• Magnetic resonance imaging (MRI) provides a more accurate
assessment and earlier detection of lesions than radiography does
Radiographic imaging: the ‘gold standard’ for assessment of disease progression in rheumatoid arthritis. Rheumatology
(Oxford). 2000 Jun. 39 suppl 1:9-16.

32. Diagnosis- CRITERIA

33. Treatment
• DMARDS - Patients with mild disease and normal radiographic
findings can begin treatment with hydroxychloroquine sulfasalazine,
or minocycline, although methotrexate also is an option.
• Patients with more severe disease or radiographic changes should
begin treatment with methotrexate.
• If symptoms are not adequately controlled, leflunomide,
azathioprine, or combination therapy (methotrexate plus one of the
newer agents) may be considered

34. NSAIDS..because they do not alter the disease course, they should not
be used alone. Patients with rheumatoid arthritis are almost two times
more likely to have serious complications from NSAID use than patients
with osteoarthritis, and they should be observed closely for symptoms
of gastrointestinal side effects
GLUCOCOTICOIDS .. The American College of Rheumatology (ACR)
guidelines recommend that patients being treated with glucocorticoids
take 1,500 mg of calcium and 400 to 800 IU of vitamin D daily
American College of Rheumatology Subcommittee on Rheumatoid Arthritis Guidelines. Guidelines for the
management of rheumatoid arthritis: 2002 update. Arthritis Rheum 2002;46:328-46.

35. DURATION OF TREATMENT
• Rheumatoid arthritis is a lifelong illness.
• Combinations of methotrexate and the new biologic agents can lead to
remission in 30 to 40 percent of patients with rheumatoid arthritis, but for
most patients, significant disease persists despite treatment.
• Complete remission rarely occurs.
In clinical trials, improvement has been tracked using the ACR improvement
criteria, most often ACR 20, ACR 50, or ACR 70.
• The numbers represent the percentage of improvement in the following
criteria: number of tender joints, number of swollen joints, global disease
activity, pain level, physical disability score, and acute phase response (as
measured by CRP or ESR).

36. Rheumatoid nodules
• Seen in 20-30% of patients with RA and associated with aggressive disease
• An extraarticular process found most commonly on extensor surfaces at
sites of frequent mechanical irritation over IP joints, over olecranon, and
over ulnar border of the forearm
• Rheumatoid factor is almost high in RN and when its negative the
diagnosis is almost improbable
• patients complain of pain and cosmetic concerns
• Treatment - non operative-steroid injection
operative surgical excision
Rheumatoid nodules : differential diagnosis and immunological findings :annals of the rheumatic
diseases 1993;52 625-626

37. Arthritis mutilans
• A form of chronic rheumatoid arthritis in which osteolysis
occurs with extensive destruction of the joint cartilages
and bony surfaces with pronounced deformities, chiefly of
the hands and feet; similar changes occur in some cases of
psoriatic arthritis.
• Digits develop gross instability with bone loss
• Treated with interposition bone grafting and fusion

38. Ulna drift at MCP
• Current mechanical factors that are postulated to play a role
secondary to joint synovitits :
i) failure of the collateral ligaments,
ii) intra-articular pressure changes,
iii) degenerative changes in the carpal and metacarpal
anatomy,
iv) muscle hypoxia induced changes in wrist tension,
v) exacerbating activities of daily living
Biomech. 2015 Feb 26;48(4):725-8.jbiomech.2014.12.052. Epub 2015 Jan 5.
Ulnar drift in rheumatoid arthritis: a review of biomechanical etiology. Morco S, Bowden A

39. Treatment of ulna drift
• Synovectomy, extensor tendon centralization, and intrinsic release
Arthroplasty
• Silicone MCP arthroplasty is most common
• Indicated for late disease
• Techniques -important to correct wrist deformity at same
time if it is radially deviated

40. Boutonneire defomity
• Treatment of boutonniere finger is individualized and is based on the
patient's current level of function, deformity, medical status, limitations of
the surgeon, and expectations
• A Corticosteroid injection is useful if active PIP joint synovitis is present.
• Surgical: Tenotomy of the terminal extensor tendon and reconstruction of
the central slip.
• PIP arthrodesis
• The choice of surgical treatment
is based on the flexibility of the PIP
joint and the status of the articular cartilage.

41. Swan neck deformity
• The deformity is the end result of synovitis of the joints, tendon
sheaths, and ligaments, which disrupts the balance of flexion and
extension forces across a joint and results in deformity, weakness,
and loss of function

42. • Nonsurgical treatment: Extension block splinting.
• Surgical: procedures that limit PIP joint hyperextension and restore DIP
joint extension
DIP joint arthrodesis,
tenodesis of the flexor digitorum superficialis,
reconstruction of the oblique retinacular ligament
volar PIP joint dermodesis,
lateral band translocation.
In late-stage disease, soft-tissue procedures alone may not result in lasting
correction of deformity.

43. WRIST –caput ulna syndrome
Pathoanatomy
• Synovitis in the DRUJ > ECU subsheath stretching > ECU
subluxation > supination of the carpal bones away from the
head of the ulna > volar subluxation of the carpus away
from the ulna > increased pressure over the extensor
compartments > tendon rupture
Early synovectomy of the radiocarpal and DRUJ can be done as
an open procedure or, when extensor tendon synovitis is absent,
as an arthroscopic procedure

44. Treatment of manifest caput ulnae syndrome,
Resection of the ulnar head together with a dorsal wrist stabilization is
indicated.
Less often, arthrodesis of the DRUJ with segmental resection of the ulna or
an arthroplasty are indicated. (Sauvé-Kapandji)
When choosing the procedure, the type and stage of wrist changes have to
be considered.
The DRUJ usually has to be treated together with the radiocarpal joint. Its
isolated treatment is rarely indicated
Orthopade. 2004 Jun;33(6):692-7. The caput-ulnae-syndrome. Pathogenesis, clinic and therapy Borisch N, Haussmann P

45. Radiocarpal Destruction
Synovitis and capsular distension leads to supination, radial
deviation, and ulnar and volar translocation of the carpus on the
radius; this causes ulnar deviation of the fingers at the MP joints
creating the classic zigzag deformity
Treatment
• Synovectomy for early disease
• Transfer of ECRL to ECU to diminish deforming forces
(Clayton's procedure)
• Radiolunate fusion (Chamay) for intermediate disease

46. RHEUMATOID ELBOW

47. • Synovitis- swelling and pain- may develop FFD due to holding in
flexed position
• Annular ligament may rupture- anterior displacement of radial head
due to pull of biceps
• Collateral ligaments may rupture ML instability
• Ulna nerve neuropathy secondary to synovitis and rheumatoid
nodule
• Cartilage and bone destruction- severe cartilage damage causing
instability and bony destruction

48. Treatment options
• Synovectomy +/- radial head excision
• Arthrodesis / Resection arthroplasty
• Arthroplasty= non constrained, semiconstrained and constrained
Indications :pain, loss of motion and instability
Semiconstrained device has best results
Reliable procedure for advanced RA of elbow

50. Shoulder conditions
RA is most prevalent form of inflammatory process affecting the
shoulder with >90% developing shoulder symptoms
Commonly associated with rotator cuff tears
Classic radiographic findings include
• Central glenoid wear
• Periarticular osteopenia
• Cysts

51. • Nonsurgical management is the primary treatment, including
pharmacologic and physical therapy regimens for patients with mild
symptoms and functional disability.
• Surgical intervention is indicated in patients with significant pain and
functional limitation when nonsurgical treatment fails to provide relief.
• The procedure selected depends on careful assessment of the degree of
articular cartilage injury and compromise of the periarticular soft tissues
• Rheumatoid Arthritis of the Shoulder Chen, Andrew L. MD, MS; Joseph, Thomas N. MD; Zuckerman, Joseph D. MD AAOS Journal of the
American Academy of Orthopaedic Surgeons: January/February 2003 - Volume 11 - Issue 1 - p 12–24

53. Knee RA
• Pathoanatomy as described above
• Surgical options
• Synovectomy of knee
• Decreases pain and swelling but does not alter prevent
radiographic progression and does not prevent the need for
TKA in the future
• Normal synovium reforms, but degenerates to rheumatoid
synovium over time
• Range of motion is not improved

54. • In advanced disease, TKA has proven to be the most successful
intervention that reduces knee pain and improves physical
function in rheumatoid arthritis patients.
• However, as rheumatoid arthritis patients carry additional
potential for late complications, many important considerations
regarding preoperative evaluation and surgical technique must be
taken into account in order to improve the results of total knee
arthroplasty in this subgroup of patients.
• Resurfacing of the patella during total knee arthroplasty

55. • The life span of RA patients with a knee replacement is not well
known, however, assuming that RA patients have a normal life span, a
TKA in this subgroup of patients on average needs to last longer and
accordingly, the potential risk of late complications increases
• Many authors also expressed concern that late failure of the PCL
could lead to late posterior instability.

56. Foot and Toe
Usually bilateral and symmetric
Forefoot joints are the first to be affected
• Toe hyperextension deformity
The earliest manifestation of RA of the forefoot is synovitis of the MTP joints
with eventual hyperextension deformity of the MTP joints including distal
migration of the forefoot pad, painful plantar callosities and skin ulcerations
over bony prominences.
• Rx: Arthrodesis of the 1st MTP joint and lesser MTP joint resections
• Talonavicular arthritis
Common to have degenerative changes
Treatment - fusion

57. HIP

59. Tendon problems
• Extensor tenosynovitis is a common presenting upper extremity
problem and, unless it resolves with medical management,
preventative tenosynovectomy is indicated to prevent tendon
rupture.
• When a rupture has occurred,
tendon reconstruction with either
a transfer or a graft has a reasonable
chance of restoring function as long
as the number of tendons involved is limited.

60. • Rupture of a single extensor tendon requires surgical treatment to
eliminate the cause and prevent further damage, as well as repairing
the injured tendon.
• Extensor Tendon Rupture
• Frequency EDM > EDC (ring) > EDC (small) > EPL
• Treatment - tendon transfer, interposition graft, or Darrach's procedure

61. • Mannerfelt syndrome -rupture of FPL in carpal tunnel due to
scaphoid osteophytes
FDS to FPL tendon transfer
• Vaughan-Jackson syndrome -describes the rupture of the hand digital
extensor tendons which occur from the ulnar side of the wrist first
then moves radially
EIP to EDC transfer and distal ulna resection
Hand Clin. 1996 Aug;12(3):551-9. Extensor tendon problems in rheumatoid arthritis. Wilson RL, DeVito MC

62. References
• National institute of Arthritis and Musculoskletal and Skin diseases. Autoimmune Diseases
• Apleys System of Orthopaedics and fractures page 59 -76
• Historical Perspective on the Etiology of Rheumatoid Arthritis Pouya Entezami, BS, David A. Fox,
MD, Philip J. Clapham, BS, and Kevin C. Chung, MD, MS
• MacGregor AJ, Snieder H, Rigby AS, et al. Characterizing the quantitative genetic contribution to
rheumatoid arthritis using data from twins. Arthritis Rheum 2000;43:30-7.
• Wellcome Trust Case Control Consortium. Genome-wide association study of 14,000 cases of
seven common diseases and 3,000 shared controls. Nature 2007; 447:661-78
• Scher JU, Ubeda C, Pillinger MH, et al. Characteristic oral and intestinal microbiotain rheumatoid arthritis (RA): a
trigger for autoimmunity? Arthritis Rheum 2010;62:Suppl:1390. abstract
• Szekanecz Z, Pakozdi A, Szentpetery A, Besenyei T, Koch AE. Chemokines and angiogenesis in rheumatoid arthritis.
Front Biosci (Elite Ed) 2009;1:44-51.
• Polzer K, Baeten D, Soleiman A, et al.Tumour necrosis factor blockade increases lymphangiogenesis in murine and
human arthritic joints. Ann Rheum Dis 2008;67:1610-6.

63. • Visser H, le Cessie S, Vos K, Breedveld FC, Hazes JM. How to diagnose rheumatoid arthritis early: a
prediction model for persistent (erosive) arthritis. Arthritis Rheum 2002;46:357-65
• Schett G, Teitelbaum SL. Osteoclasts and arthritis. J Bone Miner Res 2009;24:1142-6.
• Schett G, Stach C, Zwerina J, Voll R, Manger B. How antirheumatic drugs protect
joints from damage in rheumatoid arthritis. Arthritis Rheum 2008;58:2936-48
• Jimenez-Boj E, Redlich K, Turk B, et al. Interaction between synovial inflammatory
tissue and bone marrow in rheumatoid arthritis. J Immunol 2005;175: 2579-88
• Radiographic imaging: the ‘gold standard’ for assessment of disease progression
in rheumatoid arthritis. Rheumatology (Oxford). 2000 Jun. 39 suppl 1:9-16
American College of Rheumatology Subcommittee on Rheumatoid Arthritis
Guidelines. Guidelines for the management of rheumatoid arthritis: 2002 update.
Arthritis Rheum 2002;46:328-46
• Rheumatoid nodules : differential diagnosis and immunological findings :annals
of the rheumatic diseases 1993;52 625-626

64. • Biomech. 2015 Feb 26;48(4):725-8.jbiomech.2014.12.052. Epub 2015 Jan 5.
Ulnar drift in rheumatoid arthritis: a review of biomechanical etiology. Morco S, Bowden A
• Orthopade. 2004 Jun;33(6):692-7. The caput-ulnae-syndrome. Pathogenesis, clinic and therapy Borisch N,
Haussmann P
• Rheumatoid Arthritis of the Shoulder Chen, Andrew L. MD, MS; Joseph, Thomas N. MD; Zuckerman, Joseph
D. MD AAOS Journal of the American Academy of Orthopaedic Surgeons: January/February 2003 - Volume 11
- Issue 1 - p 12–24
• Total shoulder replacement in rheumatoid disease A 16- TO 23-YEAR FOLLOW-UP H. M. Betts, R. Abu-
Rajab,T. Nunn, A. J. Brooksbank JBJS
• Cemented Versus Cementless Total Hip Replacements in Patients Fifty-five Years of Age or Older with
Rheumatoid Arthritis By Keijo T. M¨akel¨a, MD, PhD, Antti Eskelinen, MD, PhD, Pekka Pulkkinen, PhD, Et al A
multicenter study
• Cervical spondylosis stenosis and rheumatoid arthritis- Mathew mcdowell MD and Philip lucas MD
• Hand Clin. 1996 Aug;12(3):551-9. Extensor tendon problems in rheumatoid arthritis. Wilson RL, DeVito MC