The document provides an overview of the musculoskeletal system, detailing the types of bones, their cell types, and the various joint categories. It introduces rheumatoid arthritis (RA) as a common autoimmune inflammatory condition, discussing its prevalence, clinical features, pathophysiology, diagnosis, and treatment options, including DMARDs and biologics. RA's impact on quality of life and associated comorbidities, such as increased mortality, are highlighted, along with prognostic factors influencing disease progression.

1. RA Ndlovu

2. INTRO
The musculoskeletal system is responsible for:
✓ movement of the body,
✓ provides a structural framework to protect internal organs,
✓ acts as a reservoir for storage of calcium and phosphate in the regulation of
mineral homeostasis.

3. BONES
Bones fall into two main types based on their embryonic development.
✓Flat bones, such as the skull, develop by intramembranous ossification, in which
embryonic fibroblasts differentiate directly into bone within condensations of
mesenchymal tissue during early fetal life.
✓Long bones, such as the femur and radius, develop by endochondral ossification
from a cartilage template.

4. ..
The normal skeleton has two forms of bone tissue;
✓Cortical bone, formed from Haversian systems is dense and forms a hard envelope
around the long bones
✓Trabecular or cancellous bone, fills the centre of the bone and consists of an
interconnecting meshwork of trabeculae, separated by spaces filled with bone
marrow.

5. MAIN CELL TYPES IN BONE
Osteoclasts: multinucleated cells of haematopoietic origin, responsible for bone
resorption.
Osteoblasts: mononuclear cells of mesenchymal origin, responsible for bone
formation.
Osteocytes: these differentiate from osteoblasts during bone formation and become
embedded in bone matrix.

6. JOINTS
Bones are linked by joints.
There are three main subtypes:
✓fibrous,
✓ fibrocartilaginous
✓synovial

7. TYPES OF JOINTS
Type Range of movement Examples
Fibrous Minimal Skull sutures
Fibrocartilaginous Limited Symphysis pubis
Costochondral junctions
Intervertebral discs
Sacroiliac joints
Synovial Large Most limb joints
Costal vertebral
Temporal-mandibular

8. RHEUMATOID ARTHRITIS

9. INTRO..
❑Rheumatoid arthritis (RA) is the most common persistent inflammatory arthritis,
occurring throughout the world and in all ethnic groups.
❑The prevalence is lowest in black Africans and Chinese, and highest in Pima Indians.
❑It is an auto immune condition.

10. ..
❑The clinical course is prolonged, with intermittent exacerbations and remissions.
❑Patients with RA have an increased mortality when compared with age-matched
controls, primarily due to an increased risk of cardiovascular disease.
❑This is most marked in those with severe disease, with a reduction in expected
lifespan by 8–15 years.
❑Around 40% of RA patients are registered as disabled within 3 years of onset, and
around 80% are moderately to severely disabled within 20 years.

11. PATHOPHYSIOLOGY
❑Genetic, epigenetic and environmental factors are implicated in the pathogenesis of
RA.
❑It has long been thought that RA may be triggered by an infectious agent in a
genetically susceptible host, but a specific pathogen has not been identified.
❑ Periodontal disease and oral pathogens have been implicated, as have
gastrointestinal organisms, and viruses such as Epstein–Barr and cytomegalovirus.

12. ..
❑ Cigarette smoking is a strong risk factor for developing RA, especially in people
with HLA-DR4, and is also associated with greater disease severity and reduced
responsiveness to DMARD and biological treatment.
❑ Susceptibility is increased postpartum and by breastfeeding, indicating that
hormone/immune interactions may be important.

13. ..
❑The clinical onset of RA is characterised by infiltration of the synovial membrane
with lymphocytes, plasma cells, dendritic cells and macrophages.
❑CD4+ T lymphocytes, including Th1 cells and Th17 cells play a central role by
interacting with other cells in the synovium.
❑ Lymphoid follicles form within the synovial membrane in which T cell–B cell
interactions lead B cells to produce cytokines and autoantibodies, including RF and
ACPA.

14. ..
❑Synovial macrophages are activated by immune complexes and local damage-
associated molecules acting to produce proinflammatory cytokines, including TNF, IL-
1, IL-6 and IL-15.
❑These act on synovial fibroblasts, to promote swelling of the synovial membrane and
damage to soft tissues and cartilage.

15. ..
❑The RA joint is hypoxic and this promotes new blood vessel
formation(neoangiogenesis).
❑Thus the inflamed synovium becomes vascularised, with highly activated endothelial
cells supporting the recruitment of yet more leucocytes to perpetuate the
inflammatory process.
❑Amongst the range of inflammatory mediators present in the RA joint, TNF plays an
important role by regulating production of other cytokines.

16. CLINICAL FEATURES
The typical presentation is with;
✓ joint pain
✓joint swelling
✓stiffness affecting the small joints of the hands, feet and wrists
✓Large joint involvement, systemic symptoms and extra-articular features may also
occur.

17. O/E
❑Typical features of symmetrical swelling of the MCP and PIP joints.
❑Joints are tender on pressure when actively inflamed and have stress pain on
passive movement.
❑ Erythema is unusual and its presence suggests coexistent sepsis.

18. DEFORMITIES- HAND
❑Swan neck’ deformity
❑The boutonnière or ‘button hole’ deformity
❑ The Z deformity of the thumb
❑Dorsal subluxation of the ulna at the distal radio-ulnar joint

19. BUTONNAIRE DEFORMITY

20. SWAN NECK DEFORMITY

21. COMBINATION OF HAND DEFORMITIES

22. DEFORMITIES- FOOT/LEG
❑Dorsal subluxation of the MTP joints may result in ‘cock-up’ or hammer toe
deformities.
❑In the hindfoot, calcaneovalgus (eversion).This is often associated with loss of the
longitudinal arch (flat foot) due to rupture of the tibialis posterior tendon.
❑Popliteal (‘Baker’s’) cysts may occur

23. FEET DEFORMITIES

24. EXTRA ARTICULAR MANIFESTATIONS
Systemic
✓ Fever and weight loss
✓ Fatigue
✓Susceptibility to infection
Musculoskeletal
✓ Muscle-wasting
✓ Tenosynovitis
✓ Osteoporosis
Haematological
✓Anaemia
✓ Thrombocytosis
✓Eosinophilia

25. CONT…
Cardiac
✓Pericarditis, Myocarditis and Endocarditis
✓ Conduction defects
Pulmonary
✓Pleural effusions
✓Fibrosing alveolitis
✓ Bronchiolitis
Neurological
✓Cervical cord compression
✓ Compression neuropathies
✓Peripheral neuropathy

26. ..
Lymphatic
✓Felty’s syndrome
✓ Splenomegaly
Nodules
✓Sinuses
✓Fistulae
Ocular
✓Episcleritis and Scleritis
Vasculitis
✓ Digital arteritis
✓Ulcers
✓ Pyoderma gangrenosum

27. INVESTIGATIONS
❑The diagnosis of RA is based on clinical grounds but investigationsare useful in confirming the
diagnosis and assessing disease activity
❑ The ESR and CRP are usually raised but normal results do not exclude the diagnosis.
❑ACPA are positive in about 70% of cases and are highly specific for RA, occurring in many
patients before clinical onset of the disease.
❑RF is positive in about 70% of cases, many of whom also test positive for ACPA.
❑Ultrasound examination and MRI are not routinely required in patients with obvious clinical
signs
❑Plain X-rays of the hands, wrist and feet are of limited value in early RA but certain changes
are characteristic, including periarticular osteoporosisand marginal joint erosions.

28. EUROPEAN LEAGUE AGAINST RHEUMATISM/AMERICAN
COLLEGE OF RHEUMATOLOGY DIAGNOSTIC CRITERIA
Criterion Score
Joints affected
1 large joint 0
2–10 large joints 1
1–3 small joints 2
4–10 small joints 5
Serology
Negative RF and ACPA 0
Low positive RF or ACPA 2
High positive RF or ACPA 3

29. CONT..
Duration of symptoms Score
<6 wks 0
>6 wks 1
Acute phase reactants
Normal CRP and ESR 0
Abnormal CRP or ESR 1
Patients with a score>=6 are considered to have definite RA

30. TREATMENT
❑The mainstay of treatment in RA comprises the early use of small-molecule disease-
modifying antirheumatic drugs (DMARDs), and corticosteroids for induction of
remission.
❑Early use of DMARD therapy improves clinical outcome in RA.
❑Partial or nonresponse to DMARD therapy should prompt escalation of the dose or
use of an additional DMARD, with progression to biological drugs if necessary

31. ..
❑Regular monitoring of DMARD therapy is essential because of the risk of liver and
haematological toxicity.
❑Some DMARDs are contraindicated in pregnancy especially during the first trimester
❑ Patients who wish to become pregnant should be counselled to stop DMARD
treatment while they try to conceive.

32. DMARDS
❑Methotrexate is the anchor DMARD in RA.
❑Sulfasalazine (SSZ) is widely used, both alone and in combination with methotrexate
and other drugs.
❑Hydroxycholoroquine is given usually in combination with other DMARDs.
❑Leflunomide can be used alone or in combination with other drugs.

33. CORTICOSTEROIDS
❑Systemic corticosteroids have disease-modifying activity, but their primary role is in
the induction of remission in patients with early RA who are starting synthetic DMARD
treatment.
❑Intramuscular steroids are often used to treat flares of disease activity in patients
who are established on DMARD therapy.
❑In the context of RA, osteoporosis is probably the most important SE since this is a
known complication of RA

34. BIOLOGICS
❑The use of biological agents (often abbreviated to ‘biologics’)is reserved for the
treatment of patients who have high disease activity despite having had an
adequate trial of traditional DMARDs.
❑These agents are targeted towards specific cytokines and other cell surface
molecules regulating the immune response.
❑Biological treatment is more effective than standard DMARD therapy, treatment but
costs are significantly greater and increase chances of infection since they suppress
the immunity

35. EXAMPLES
Rituximab
Abatacept
Anakinra
Tocilizunab

36. OTHER TREATMENT MEASURES
Surgery
General measures;
✓ Physical rest,
✓ analgesics and NSAID may be required to control symptoms.
✓Passive exercises and joint protection measures
✓ In the vast majority, management is outpatient but hospital admission can be helpful in
patients with very active disease for a period of bed rest, multiple joint injections, splinting,
regular hydrotherapy, physiotherapyand education.

37. PROGNOSIS
Factors that associate with a poorer prognosis are;
✓ disability at presentation,
✓female gender,
✓ involvement of MTP joints,
✓radiographic damage at presentation,
✓smoking
✓positive RF or ACPA.

38. AHSANTENI SANA