For Phase 2 Katie Knappett Phase 3B The Peer Teaching Society is not liable for false or misleading information…

For Phase 2

Katie KnappettPhase 3B

The Peer Teaching Society is not liable for false or misleading information…

• Go over basic sciences from Phase 1• Aetiology / Risk Factors• Pathophysiology• Epidemiology• Clinical Presentation• Diagnostic Tests• Treatment


Aims

• Osteoarthritis• Rheumatoid Arthritis• SLE• Seronegative Spondyloarthropathies• Crystal Arthropathies


Conditions

Rheumatic diseases:• Joints• Connective Tissues

• Immunology


“Rheumatology”


Joint Pain


Synovial Joints

• Most common type of arthritis• Age-related; degenerative• Synovial joints affected

• Epidemiology– Prevalence increased with age. Uncommon <45– Familial


Osteoarthritis

• Age• Sex (F>M)• Genetic predisposition (polyarticular)

• Obesity• Local factors– Abnormal biomechanics– Occupation (farming, footballer…)


Risk Factors for OA

• There is a difference between structural OA and symptomatic OA


Pathogenesis of OA

Symptoms•Joint pain•Stiffness•Gelling•Instability•Loss of function•Worse in evening


Clinical Features of OASigns

•Tenderness•Swelling•Limited ROM•Crepitus•Joint instability•Bony swelling (Heberden’s Nodes, DIPJ)•Muscle wasting•Altered gait


• Bloods – ESR normal, hsCRP may be raised. RF and ANA negative.

• X-Rays – abnormal only when advanced• MRI – subchondral bone changes, early

cartilage injury• Arthroscopy• Aspiration of synovial fluid – viscous fluid with

few leucocytes


Investigations


OA X-Ray shows LOSS

Loss of joint space

Osteophyte formation

Subchondral cysts

Subarticular sclerosis


Management of OA

Non-Pharmacological

Pharmacological

Surgical- Low impact activity- Weight loss- Physiotherapy

- Analgesia-Regular Paracetamol (1g QDS)-NSAIDs PRN (+PPI if regular)

- Joint Replacement

• Inflammatory• Autoimmune disease• Chronic symmetrical, deforming, polyarthritis

of synovial joints• Systemic involvement

• Typically female patients aged 30-50


Rheumatoid Arthritis

• Female sex• Genetic predisposition• Smoking


Risk Factors for RA

• Widespread persistent synovitis • Synovial hypertrophy• Synovial proliferation• Inflammatory infiltration• “Pannus” of inflamed synovium • Damages underlying articular cartilage by

blocking nutrition / direct cytokine effect• Cartilage becomes thinned & bone is exposed


Pathophysiology of RA

Slowly progressive, symmetrical, peripheral polyarthritis evolving over weeks – months.


Clinical Features of RA

Symptoms•Pain & Stiffness typically in the morning•Tiredness•Systemically unwell•Disturbed sleep

Signs•Inflammation

• Redness• Heat• Swelling• Pain

•Limited ROM•Muscle wasting•Deformities


Deformities in RA

Ulnar Deviation

Z Thumb

Boutonniere & Swan neck deformities

Joint Subluxation(wrist/MCPJ)

Muscle Wasting


– Subcutaneous nodules– Firm, intradermal– Occur over pressure points (elbows, finger joints,

Achilles tendon)


Rheumatoid Nodules

Ring of macrophages and fibroblasts

Cuff of connective tissue containing lymphocytes and

plasma cells

Necrotic centre


Extra-Articular Features of RA• RA is a SYSTEMIC disease


Investigations-Bloods

- Raised ESR- Normocytic anaemia- RF may be negative at the start, becoming positive in 80%- ANA +ve in 30%- Anti-CCP

-X-rays- Decreased joint space- Bony erosions- Subluxation- Carpal destruction


Management of RANon-Pharmacological Pharmacological

Surgical

- Regular exercise- Physiotherapy-Occupational therapy- Orthotics (e.g. wrist splint)

-NSAIDs- Ibuprofen- Consider COX II selective if needing max doses (e.g. Celecoxib)- PPI cover

- Steroids- Intra-articular- Systemic

- DMARDS

- Joint replacement- Pain relief, improve function

• Problem: Inflammation• Solution : Stop the inflammation!


Disease-Modifying Drugs (DMARDs)

Sulfasalazine MethotrexateCiclosporinGoldAzathioprinePenicillamineHydroxychloroquine

Sulfasalazine MethotrexateCiclosporinGoldAzathioprinePenicillamineHydroxychloroquine

Biologics:-Anti-cytokine treatments

- Infliximab (anti -TNF-α antibody)- Etanercept (TNF-α receptor blocker)

Biologics:-Anti-cytokine treatments

- Infliximab (anti -TNF-α antibody)- Etanercept (TNF-α receptor blocker)


RA vs OA


RA vs OARheumatoid

ArthritisOsteoarthritis

Pain Eases with use Increases with use

Stiffness Significant (>60 mins)Early morningAfter rest

Not prolonged (<30 mins)Morning/Evening

Swelling Synovial +/- bony Bony / None

Inflammation Hot, red joints No inflammation

Demographics Young, FH Older, occupation

Joint distribution Small jointsHands & feet

1st CMCJ, DIPJKnees

NSAIDs Good response Less convincing response

• Inflammatory multisystem disorder

• Autoantibody (ANA)• Deposition of immune

complexes

Most common Sx – rash & arthralgiaMost serious Sx – renal & cerebral involvement


Systemic Lupus Erythmatosus

• Afro-Caribbean / Asian ethnicity• Female: Male ratio is 9:1• Peak age onset 20-40


SLE Epidemiology

• ? Cause• Predisposing Factors– Genetics (HLA A1, B8, DR3; Complement

deficiencies, Family history)– Sex Hormone Status (Premenopausal women,

XXY, HRT can cause flare up)– Drugs (hydralazine, isoniazid, penicillmine can

cause mild SLE)– EBV ?trigger for SLE


SLE Aetiology

• Cells die by apoptosis; self-antigens presented to immune system for phagocytosis– Antibodies to these self-antigens are produced– Immune system fails to inactivate B and T cells

responding to these self-antigens• Autoantibody production • Complement activation• Neutrophil influx• Inflammation• Abnormal cytokine production


SLE Pathophysiology

• Skin/Kidneys– Deposition of complement and IgG antibodies– ↑ neutrophils and lymphocytes– Vasculitis

• Joints– Immune complexes deposited in synovium


SLE Pathology


SLE Clinical Features- Great variety!- Most patients: fatigue, arthralgia, skin involvement- Major organ involvement is less common, but more serious

- Great variety!- Most patients: fatigue, arthralgia, skin involvement- Major organ involvement is less common, but more serious

SKIN>85% of cases

“Butterfly” erythema

PhotosensitivityMalar/Discoid rashLivedo reticularis

Raynaud’sAlopecia

JOINTS/MUSCLES>90% have joint involvement

Like RA – symmetrical small jointsPainful but clinically normal

Deformity is RARE

HEART/CVS25% of casesPericarditis

Pericardial effusionsMyocarditis

Cardiomyopathy↑IHD/Stroke

Antiphospholipid syndrome

LUNGS>50% of cases

Recurrent pleurisyPleural effusions

PneumonitisPulmonary fibrosis

Intrapulmonary haemorrhage

(vasculitis)

KIDNEYS30% of cases

Lupus NephritisGlomerulonephritis

NERVOUS SYSTEM60% of casesDepression

Severe psychiatric disturbanceEpilepsy

Migraines


SLE Clinical Features

ORDERHISANA

ORDERHISANA

Oral ulcersRash (malar)Discoid rash

Eye involvementRenal disorders /

recurrent abortionHaematologicalImmunological

SerositisArthritis

Neurological involvementAlopecia

Oral ulcersRash (malar)Discoid rash

Eye involvementRenal disorders /

recurrent abortionHaematologicalImmunological

SerositisArthritis

Neurological involvementAlopecia

Diagnostic Criteria1.Malar (butterfly) rash2.Discoid rash3.Photosensitivity4.Oral ulcers5.Arthritis6.Serositis (pleutiris / pericarditis)7.Renal disorders (persistent proteinuria)8.CNS disorders (seizures / psychosis)9.Haematological disorders (haemolytic anaemia, leukopenia, lymphopenia, thrombocytopenia)10.Immunological disorders (Antiphospholipid antibody, anti-DNA antibody, anti-SM antibody)11.Antinuclear antibody positive in 95%

Diagnostic Criteria1.Malar (butterfly) rash2.Discoid rash3.Photosensitivity4.Oral ulcers5.Arthritis6.Serositis (pleutiris / pericarditis)7.Renal disorders (persistent proteinuria)8.CNS disorders (seizures / psychosis)9.Haematological disorders (haemolytic anaemia, leukopenia, lymphopenia, thrombocytopenia)10.Immunological disorders (Antiphospholipid antibody, anti-DNA antibody, anti-SM antibody)11.Antinuclear antibody positive in 95%


SLE InvestigationsRoutine Bloods

Low WCC (neutophils and lymphocyres)

Low plateletsNormocytic anaemia/Haemolytic anaemia

Raised ESRNormal CRP

Raised Urea and Creatinine in renal

involvement

Autoantibodies

ANAAnti-dsDNA

Anti-RoAnti-LaAnti-SM

Antiphospholipid antibodies (in APS)

Complement↓ C3 and C4

HistologySkin/Renal biopsy –

deposition of IgG and complement

complexes

ImagingCT Head – infartcs/

Haemorrhage/ cerebral atrophy


Management of SLENon-Pharmacological

Pharmacological

- Avoidance of sunlight / sunblock-Reduce CV Risk factors-Rheum referral

- NSAIDs for arthralgia, serositis- Hydroxychloroquine for joint/skin problems if NSAIDs insufficient. - High dose prednisolone for severe episodes. Other immunosuppresives/steroid sparing agents (cyclophosphamide, azathioprine, methotrexate) can be used.- Longterm anticoagulant in APS

Surgical

- Renal transplant


Prognosis of SLE• Episodic relapsing/remitting course• 10 year survival 90%• Deaths <age 50 usually due to cerebral/renal

involvement, or infection• >50, deaths due to stroke / CAD• Increased lymphoma risk• Fertility usually normal though increased

miscarriages

• Familial; HLA-B27• Different distribution of joint involvement– Spine/Sacroiliac joints– Asymmetrical large joint oligo- or monoarthropathies

• Enthesitis (inflammation of site of attachment of tendon/ligament to bone)

• Extra-articular features• No RF production (“Seronegative”)


Seronegative Spondyloarthropathies

• 3 main conditions– Ankylosing Spondylitis– Psoriatic Arthritis– Reactive Arthritis


Seronegative Spondyloarthropathies

• Inflammatory spinal disorder• Affects young adults• Men present earlier– M:F age 16 is 6:1– M:F age 30 is 2:1

• 95% are HLA-B27 +ve


Ankylosing Spondylitis


Clinical Features of ASEarly Features / Presentation

-Typically young male-Low back pain / stiffness

-Buttock pain-Worse in the morning; relieved by exercise

-Episodic but persistent for 3/12

Early Features / Presentation-Typically young male

-Low back pain / stiffness-Buttock pain

-Worse in the morning; relieved by exercise-Episodic but persistent for 3/12

Late Features-Kyphosis

-Neck hyperextension (question mark posture)-Spino-cranial ankylosis

Late Features-Kyphosis

-Neck hyperextension (question mark posture)-Spino-cranial ankylosis

Associations

-Chest pain-Hip involvement

-Knee involvement-Enthesitides – plantar

faciitis- Crohn’s/UC/Amyloid

-Psoriaform rashes-Iritis / sterile uveitis

Associations

-Chest pain-Hip involvement

-Knee involvement-Enthesitides – plantar

faciitis- Crohn’s/UC/Amyloid

-Psoriaform rashes-Iritis / sterile uveitis

• High sensitivity and specificity• 3 out of the following in adults under 50

indicates AS:– Morning stiffness >30 mins– Improvement with exercise but not rest– Awakening due to back pain in the 2nd half of the

night only– Alternating buttock pain


Classification Criteria

• Clinical diagnosis• Radiological findings – – Early: Normal, or

erosions/sclerosis affecting both sides of lower sacroiliac joints

– Late: Squaring of vertebra, “bamboo spine”


AS Investigations


Management of ASNon-Pharmacological

Pharmacological

Surgical

- Exercise, not rest-Intense exercise regimens

-NSAIDs for pain / stiffness- Sulfasalazine / Methotrexate help peripheral arthritis / enthesitis-Infliximab

-Long term bisphosphontes to help prevent osteoporotic spinal fractures

- Spinal osteotomy

• Arthritis / Enthesitis in patients with psoriasis or FH or psoriasis

• Skin disease may develop after the arthrtitis

• Asymmetrical arthritis involving DIPJ and spine• Dactylitis (due to synovitis/tenosynovitis)• Arthritis mutilans


Psoriatic Arthritis

• Responds to:– NSAIDs– Methotrexate– Cyclosporin– Anti-TNFα Therapies


Psoriatic Arthritis Treatment

• Large joint mono- or oligoarthritis occurring following an infection

• Men > Women

• Typical triggers– NSU e.g. Chlamydia trachomats– Gut infections; salmonella, shigella, yersinia


Reactive Arthritis

• May be chronic or relapsing

• Management:– Rest– Splint joints– NSAIDs / Steroids– Consider sulfasalazine / Methotrexate– Treating original infection has little benefit


Reactive Arthritis

• “Reiters Syndrome”– Can’t See, Can’t Pee, Can’t climb a tree….

– Reactive Arthritis– Urethritis– Conjuncivitis


Reactive Arthritis

• Gout/Pseudogout

• 2 main types of crystal involved– Soduim Urate– Calcium pyrophosphate


Crystal Arthritis

• Inflammatory arthritis• Hyperuricaemia• Intra-articular sodium urate crystals• VERY painful


Gout

• Uric acid is the end product of purine metabolism– Blood levels depend on purine synthesis, dietary

purines and elimination of urate by the kidney/intestine

• Risk factors for hyperuricaemia (:. Gout!)– Renal function– Body weight– Blood pressure– Alcohol intake


Hyperuricaemia

• Aggressive induction/cessation of hypouricaemic therapy (Allopurinol)

• Alcohol / shellfish binges• Sepsis / MI / Acute severe illness• Truma / Surgery / Dehydration (diuretics)


Precipitants of Gout Attack

• Middle aged – older men• Sudden onset (ususally during the night)• Agonising pain• Red, shiny joint (“polished apple”)• Tender

• Chronic gout: urate deposits (tophi) found in peripheries


Clinical Features of Gout

• Clinical picture is diagnostic, as is the response to treatment

• Joint Aspiration & Microscopy of Synovial fluid – Sodium Urate seen which is “negatively birefringent needles under polarised light”

• X-Ray – soft tissue swelling, periarticular erosions, normal joint space

• Bloods – raised serum uric acid (>600µmol/L)


Investigations of Gout

• Strong NSAID e.g. naproxen Or• Colchicine Or• Steroids

• Prevent future attacks by avoiding high purine foods, alcohol XS, weight loss


Management of Acute Gout

• Reduction of serum urate with long-term Allopurinol (Inhibitor of Xanthine oxidase which converts Xanthine to Urate)

• Start alongside NSAID/Colchicine as initiation can precipitate acute attack

• Check serum urate levels and adjust dose accordingly


Recurrent Gout

• AKA Calcuim Pyrophosphate Dihydrate (CPPD) arthropathy

• Similar to gout but affects different joints; mainly wrist/knee

• More common in Women


Pseudogout

• Dehydration• Intercurrent illness• Hyperparathyroidism• Myxoedema• Low Phosphate or magnesium• Osteoarthritis• Haemochromotosis• Acromegaly


Pseudogout Risk Factors

• Diagnosis– Synovial fluid microscopy:• Positively birefringent rhomboidal crystals• Purulent aspirate

– Bloods• Raised ESR, CRP and WCC


Pseudogout

• Aspiration reduces pain• NSAID/Colchicine as with gout• Intra-articular steroid injection


Pseudogout Treatment

• Septic Arthritis• Systemic Scerosis• Polymyalgia Rheumatica• Vasculitis• Polymyositis / Dermatomyositis


Other Rheumatology not covered

Documents

For Phase 2 Katie Knappett Phase 3B The Peer Teaching Society is not liable for false or misleading information…