MSK: Part 3 Flashcards
What is Scleroderma
Systemic Scloerosis: Multisystem disease with involvement of skin and Raynauds
How does Systemic Sclerosis distinguish itself from localised scleroderma such as morphed
Latter: Do not involve organ disease and no vasospasm (Raynauds)
What gender does Scleroderma effect
Females
Peak incidence of Scleroderma
Between 30 and 50
Is Scleroderma common in children
No
Risk factors for Scleroderma
- Exposure to vinyl chloride, silica dust, adulterated rapeseed oil and trichloroethylene
- Drugs such as bleomycin
- Genetic
Pathophysiology for Scleroderma
- Widespread vascular damage involving small arteries, arterioles and capillaries is an early feature
Initial stage of scleroderma
- Initial endothelial damage with release of cytokines (endothelia-1) = VASOCONSTRICTION
What does continued vascular damage and increased vascular permeability and activation of endothelial cells lead to
- Upregulation of adhesion molecules: E-selectin, VCAM and intracellular adhesion molecule 1 (ICAM-1)
- Cell Adhesion: T and B cells, monocytes and neutrophils
- Migration of cells through leaky endothelium and into extracellular space
What do these cell-cell and cell-matrix interactions stimulate
Production of cytokines and growth factors which mediate PROLIFERATION and ACTIVATION of vascular and connective tissue cells - particularly fibroblasts
What mediators activate fibroblasts
IL1, 4, 6, 8, TGF-B and PDGF
What do fibroblasts secrete in Scleroderma
- Increased quantities of COLLAGEN TYPE I + 2
Consequence of secreted COLLAGEN TYPE I + 2
Fibrosis in lower dermis of the skin and internal organs
What is the end-product of scleroderma
- Uncontrolled and irreversible proliferation of connective tissue and thickening of vascular walls with narrowing of the lumen
- Damage to small blood vessels produces widespread obliterative arterial lesions and chronic ischaemia
Clinical presentation of Scleroderma
- RAYNAUDS
- Limited cutaneous scleroderma (CREST SYNDROME)
- Diffuse cutaneous scleroderma (30% of cases)
What is limited cutaneous scleroderma
- Starts with Raynaud’s for many years BEFORE skin changes
- Skin involvement limited to hands, face, feet and forearms
- Skin is tight over fingers and causes flexion deformities
- Face and skin produce beak-like nose and small mouth (microstomia)
- Painful digital ulcers and telangiectasia (spider veins on the skin)
- Oesophageal dysmotility or strictures
Why was it previously called CREST syndrome
- Calcinosus (calcium deposits in subcutaneous tissue)
- Raynauds
- Oesophageal Dysmotility or strictures
- Sclerodactyly (tightness of skin)
- Telenagiectasia (spider veins)
Why is Diffuse cutaneous scloerderma different to limited cutaneous scleroderma
Skin changes more rapidly and more widespread
What organs are involved in diffuse cutaneous scleroderma
- GI
- Renal
- Lung
- Heart
GI involvement in diffuse scleroderma
- Oesophagus loses strength and dilates = heartburn and dysphagia
- Small intestines loses strength and dilates = bacterial overgrowth and malabsorption
- Colon has pseudo-obstruction
Renal involvement in diffuse scleroderma
- Acute and CKD
2. Acute hypertensive crisis is a complication of renal involvement
Lung disease in diffuse scleroderma
- Fibrosis
- Pulmonary vascular disease
- Pulmonary hypertension
Herat in diffuse scleroderma
Arrhythmias and conduction disturbances due to myocardial fibrosis
Diagnostics for Scleroderma
- FBC
- Urinalysis
- CXR
- Hand X-ray
- Barium swallow
- High res CT
Test results in FBA for scleroderma
- Normochromic, normocytic anaemia
- Microangiographic haemolytic anaemia
- Urea and creatine rise in acute kidney injury
4, Autoantibodies - Rheumatoid factor positive in 30%
- ANA positive
What antibodies are found n Limited cutaneous scleroderma
- Speckled, nucleolar or ANTI-CENTROMERE ANTIBODIES (ACAs) - 70% cases
What antibodies are found in Diffuse cutaneous scleroderma
- Anti-topoisomerase-1 antibodies
2. Anti-RNA polymerase
What would urinalysis show in scleroderma
Albumin/creatinine ratio
What would CXR show in scleroderma
Exclude other pathologies (e.g. cardiomegaly)
What would hand x-ray show in scleroderma
- See deposits of calcium around fingers
What would Barium Swallow show in scleroderma
- Confirms impaired oesophageal motility
What does high res CT show in scleroderma
Confirm fibrotic lung involvement
How is scleroderma treated
NO CURE:
Raynauds: Hand warmers and ORAL VASODILATORS
Oesophagus: LANSOPRAZOLE
Nutrition supplement for malabsorption
ACE Inhibitor: RAMIPRIL
Early detection of pulmonary hypertension
What oral vasodilator is given for raynauds
Calcium channel blocker: ORAL NIFEDIPINE
Endothelia receptor antagonist: ORAL BOSENTAN
How is pulmonary fibrosis caused in scleroderma treated
IMMUNOSUPRESSION: IV CYCLOPHOSPHAMIDE
ORAL PREDNISOLONE
What is polymyositis
RARE muscle disorder of unknown aetiology in which there is inflammation and necrosis of skeletal muscle fibres
What is Polymyositis called when it effects the skin
DERMATOMYOSITIS
What organ can be effected in POLYMYOSITIS
Lungs = interstitial lung disease
What gender does polymyositis effect
Females
What viruses can cause POLYMYOSITIS
Coxsackie
Rubella
Influenza
Clinical presentation of POLYMYOSITIS
- Symmetrical progressive muscle weakness and wasting affecting muscles of shoulder and pelvic girdle
- Patients struggle squatting, going upstairs, rising from a chair and raising hands above their heads
- Pain and tenderness are uncommon
- Involvement of pharyngeal, laryngeal and respiratory muscles can lead to dysphagia and respiratory failure
Clinical presentation of DERMATOMYOSITIS
- Purple discolouration of eyelids and scaly erythematous plaques all over the knuckles (GOTTRON’s PAPULES)
- Arthralgia, dysphagia resulting from oesophageal muscle involvement and RAYNAUDS
- Increased incidence of malignancy
Diagnostics of MYOSITIS
- MUSCLE biopsy
- FBC
- Electromyography
- MRI
Role of Muscle biopsy
Shows fibre necrosis and inflammatory cell infiltrates - CONFIRMS
What would FBC show in MYOSITIS
- ESR NOT raised
- Serum antibodies:
ANA positive
Rheumatoid factor positive in 50%
Myositis-specific antibodies
What does an EMG show in MYOSITIS
Typical muscle changes
What does an MRI show for myositis
Abnormally inflamed muscles
How is MYOSITIS treated
- Bed rest helpful with excersise
- ORAL PREDNISOLONE
- HYDROXYCHLOROQUINE helps with skin disease
What early intervention can be given for MYOSITIS
- ORAL AZATHIOPRINE
- ORAL METHOTREXATE
- ORAL CICLOSPORIN
When is ORAL PREDNISOLONE STOPPED in myositis
Continued until at least 1 month after myositis has become clinically and enzymatically inactive then tapered down SLOWLY
What is RAYNAUDS PHENOMENON
- Intermittent spasms in the arteries supplying fingers and toes
What precipitates RAYNAUDS
COLD
What relives RAYNAUDS
Heat
No underlying cause vs underlying cause in Raynauds nomenclature
No underlying - RAYNDAUD’S DISEASE
Underlying - RAYNAUDS PHENOMENON
What gender does Raynauds effect
FEMALES
Pathophysiology of RAYNAUDS
Bilateral and effects fingers more than toes
Clinical presentation of RAYNAUDS
- Ischaemia causes PALLOR and CYANOSIS due to sluggish blood flow then redness due to hyperaemia (white -> blue -> red)
- Numbness, a burning sensation
- Severe pains as fingers warm
- Infarction and digital loss
- Smoking can aggravate symptoms
How is Raynauds diagnosed
- Primary causes needs to be distinguished from secondary causes
What conditions can cause Raynauds
- SLE
- Systemic Sclerosis
- RA
- DERMATOMYOSITIS
Occupation cause of raynauds
Vibrational tools
What drugs can cause RAYNAUDS
Beta-blockers
Smoking
How is RAYNAUDS treated
- Wear gloves and warm clothes
2, Stop smoking - beat blockers
- ORAL NIFEDIPINE (vasodilator)
Why is NIFEDIPINE unsuitable sometimes
Cerebral vasodilatation causes headaches
What do Seronegative spondyloarthropathies and SPONDYLOARTHRITIS
- Axial Inflammation (spine and sacroiliac joints)
- Asymmetrical peripheral arthritis
- Absence of RA (seronegative)
- Strong association with HLA B27
What type of antigen is HLA-B27
Class I surface antigen
What is a class I surface antigen
Present on all cells except RBC s
What encodes a HLA B27 gene
MHC on chromosome 6
What cells express HLA B27
APCs
Role of HLA B27
Immunity and self-recognition
What is the molecular mimicry theory of spondyloarthritis
- Infection triggers an immune response and infectious agent has peptides similar to HLA-B27 molecules = auto-immune response triggered against HLA-B27
Clinical presentation of spondyarthropathies
SPINEACHE:
- Sausage digits
- Psoriasis
- Inflammatory back pain
- NSAID good response
- Enthesitis in heel
- Arthritis
- Crohn’s/Colitis/elevated CRP (can be normal in AS)
- HLA-B27
- Eye (Uveitis)
What is Ankylosing Spondylitis
Chronic inflammatory disorder of spine, rides and sacroiliac joints
Define ankylosis
Abnormal stiffening and immobility of joint due to new bone formation
What gender does AS effect
Males
What age does AS effect
16 years - young adult
What ethnicity are most commonly effected by AS
NA
Risk factors for AS
- HLA-B27 positive
2. Klebsiella, Salmonella, Shigella
Pathophysiology of AS
- Lymphocyte and plasma infiltration occurs with local erosion of bone at the attachments of the intervertebral and other ligaments which heals with new bone formation (SYNDESMOPHYTE)
What is enthesitis
Inflammation where tendons and ligaments insert into bone
What is a syndesmophyte
New bone formation and vertical growth from anterior vertebral corners
Clinical presentation of AS
- Men less than 30 yrs
- Gradual onset of back pain, worst at night
- Spinal morning stiffness that is relieved by exercise
- Pain radiates from sacroiliac joints to hips/buttocks which improves towards end of the day
- Progressive loss of spinal movement = reduced thoracic expansion )
- Asymmetrical joint pain unlike RA
What kind of joint pain is usually seen in AS
Oligoarthritis (1 or two joints)
Tow characteristics of spinal abnormalities in AS
- Loss of lumbar lordosis (normal inward curve of spine) and increased kyphosis
- Limitation of lumbar spine motility in saggital and frontal pain
How is reduced spinal flexion in AS demonstrated clinically
SCHOBER TEST
What is the SCHOBER test
make made at 5th lumbar spinous process and 10 cm above, with patient in erect position -> on bending forward, distance should increase to more than 15 cm in normal individuals
What enthesitis is seen in SA
- Achilles tendinitis
- Plantar fasciitis
Tenderness around pelvis and chest wall
What are non-articular features of SA
- Anterior uveitis (inflammation of middle eye)
2. Osteoporosis
How is SA diagnosed
- FBC
- X-ray
- MRI
What would FBC show for SA
- ESR and CRP raised (CRP can be normal)
- Normocytic anaemia
- HLA-B27 positive (NOT DIAGNOSTIC)
What would an X-ray show for SA
- Erosion of sclerosis of margins of sacroiliac joints which proceed to ankylosis
- Blurring of upper and lower vertebral rims at the thoracolumbar junction caused by enthesitis at insertion of intervertebral ligaments
- Heals with new bone formation resulting in bony spurs (SYNDESMOPHWYTES) - progressive calcification of these can lead to bamboo spine (fusion of spinous process)
- Fusion of sacroiliac joints
What would MRI show for SA
Gadolinium shows sacrolitis before seen on X-ray
How is SA treated
- Treated quickly to prevent irreversible syndesmophyte formation and progressive calcification
- Morning excersise to maintain posture and spinal motility
- NSAIDs (IBUPROFEN) at night
- METHOTREXATE for peripheral arthritis
- TNF-alpha blocker:
infliximab, Etanercept or ADAlimumab - Local steroid injection for pain relief
- Surgery (hip replacement)
Why re TNF-alphas given for SA
Improves spinal and peripheral joint inflammation, the earlier you start the less syndesmophwytes form
Does psoriasis have to occur with Psoriatic arthritis
No
Risk factors for Psoriatic arthritis
- Family history of psoriasis
Clinical presentation for psoriatic arthritis
- Asymmetrical oligoarthritis
- Symmetrical seronegative polyarthritis (RA)
- Spondylitis
- Distal interphalangeal arthritis
- Arthritis Mutilans
Characteristics of spondylitis in psoriatic arthritis
- Unilateral or bilateral sacrolitis and early cervical spine involvement (only 50% are HLA-B27 positive)
Characteristics of distal interphalangeal arthritis in psoriatic arthritis
- DIPs involved only
- Adjacent nail dystrophy and enthesitis extending into nail root
- Dactylics (sausage fingers) in which an entire finger or toes is swollen, with joint and tendon sheath involvement
How common is arthritis mutilans in psoriatic arthritis
5% preverlance
What is arthritis mutilans
- Destruction of small bones in hands and feet
- Pencil in cup X-ray changes
- Bone respiration (periarticular osteolysis) and bone shortening
Where are hidden sites for psoriasis
- Behind and inside ears
- Scalp
- Pitting in nails and onokylisis (where nail lifts off nail bed and looks brittle and flaky)
- Umbilicus, natal cleft and penile psoriasis
Diagnostics for psoriasis
- FBC
2. X-ray
FBC results for psoriasis
- Bloods normal
2. CRP and ESR normal
What would an X-ray show in psoriasis
- Psoriatic arthritis is erosive but the erosions are central in the joint, not juxta-articular
- May be a ‘pencil in cup’ deformity in the IPJs - bone erosions create a pointed appearance and the articulating bone is concave
- Skin and nail disease can be mild and may develop AFTER arthritis
Treatment of psoriasis
- NSAIDs or analgesics (can worsen skin lesions tho)
- Intra-articular corticosteroid injections for local synovitis
- DMARDs - METHOTREXATE, SULFASALAZINE and LEFLUNOMIDE (mild)
METHOTREXATE and CYCLOSPORIN (severe)
Anti-TNF alpha agents: ETANERCEPT and GOLIMUMAB when METHOTREXATE fails
What is sidrah so fit?
she just is. jealousy is a disease bitch
What is reactive Arthritis
Sterile inflammation of the synovial membrane (synovitis), tendons and fascia triggered by an infection at a distant site, usually GI or genital
What part of the body does reactive arthritis effect
Lower-limb
What people does reactive arthritis effect
Males in HLA-B27 positive have a 50 fold risk
Main causes of reactive arthritis
- GI Infections:
Salmonella
Shigella
Yersinia Enterocolitica - Sexually acquired:
Urethritis from chlamydia trachomatis
Ureaplasma Urealyticum
Clinical presentation of Reactive Arthritis
- acute, ASYMMETRICAL, lower-limb arthritis
- Acute Anterior uveitis
- Circinate balantis: Painless ulceration of the penis
- Enthesitis: Common
- Sterile conjunctivitis in 30%
What does enthesitis of the heal do
- Causes plantar fasciitis and Achilles tendon enthesitis
What clinical features can be found in patients with reactive arthritis who are HLA-B27 positive
Sacroilitis and Spondylitis
What skin lesions resemble psoriasis
- Circinate Balanitis: In the uncircumcised male causes painless superficial ulceration of the glans
- In circumcised males, the lesion is raised, red and scaly
Both heal without scarring
Keratoderma Blennorrhagica:
Involves skin of the feet and hands, which develop painless, red and often confluent raised plaques and pustules that are histologically similar to pustular psoriasis
Nail dystrophy occurs
Diagnosis of reactive arthritis
- ESR and CRP raised in acute phase
- Culture stool if diarrhoea
- Sexual health review
- Aspirated synovial fluid is sterile with high neutrophil count:
If joint is hot and swollen can exclude crystal arthritis infection using aspiration
5. X-ray may show enthesitis
Treatment of reactive arthritis
- NSAIDs and corticosteroid injections for joint inflammation
- Treat persisting infection with antibiotics
- Screen sexual partners
- Majority of individuals with reactive arthritis have a single attack that settles but a few develop disabling relapsing and remitting arthritis
How are relapsing remitting cases of reactive arthritis treated
METHOTREXATE
SULFASALZINE
If METHOTREXATE and SULFASALAZINE are ineffective then what can we sue
TNF-alpha blockers: ETANERCEPT and GOLIMUMAB
Define Systemic Vasculitis
- Inflammation of vessel wall
- Inflammation and necrosis of blood vessel walls with subsequent impaired blood flow resulting in:
- Vessel wall destruction: aneurysm, rupture and stenosis resulting in perforation and haemorrhage into tissues
- Endothelial injury:
resulting in thrombosis + ischaemia/infarction of dependent tissues
What diseases can systemic vasculitis be seen in
- RA
- SLE
- Polymyositis
- Allergic drug reactions
How is systemic vasculitis treated
- By size of blood vessels involved and presence or absence of anti-neutrophil cytoplasmic antibodies
What does large-vessel vasculitis refer to
Aorta and major tributaries
Give examples of large-vessel vasculitis
- Giant cell arteritis/ polymyalgia rheumatic
2. Takayasu’s arteritis
What does medium-vessel vasculitis refer to
- Medium and small-sized arteries and arterioles
Examples of medium-vessel vasculitis
- Classical polyarteritis nodes
2. Kawasaki’s disease
What does small-vessel vasculitis refer to
Small arteries, arterioles, VENUES and capillaries
Examples of small-vessel vasculitis
- ANCA-associated:
- Microscopic polyangitis
- Granulomatosis with polyangitis - ANCA- negative:
- essential cryoglobulinaemia
- cutaneous lecuocytoclastic vasculitis
