Patho-3-Autoimmunity & Inflammation of MSK Flashcards
In a table compare & contrast RA, seronegative, SLE & polymyositis in terms of HLA, M:F, distribution & joint complications
Patterns of extra-articular disease for RA (x5)
- subcutaneous nodules
- lung nodules
- scleritis/episcleritis
- vasculitis
- spleen (neutropenia)
Patters of extra-articular disease for SLE (x7)
- skin & mucosa
- kidneys
- lungs
- serosa
- CNS
- thromboemoblic disease
- placenta
Patterns of extra-articular disease for Myositis (x2)
- oesophags
- pulmonary fibrosis
Patterns of extra-articular disease for seronegative arthritis
- pulmonary fibrosis
- iritis
- skin
- GI
- genitourinary
Patterns of extra-articular disease for Sjogren’s syndrome
- exocrine glands
- skin & mucosa
- nerves
- GI
RA epidemiology
- global disease
- 1% population prevalence
- more common in some ethnic groups
- increase in incidence gradual from 30-85yrs
- F > M (2:1)
Joint features for RA (x7)
- Chronic symmetrical erosive arthritis
- Pannus/Synovitis formation
- tendon subluxation
- cartilage destruction
- bone erosion
- juxta-articular osteoporosis
(Just Cracking Bones Particularly Carpals)
- functional deformity progresses to fixed deformity
T/F: 70% of people with RA will have erosions within 3 years
True
Clinical manifestations of RA
For at least 6 weeks:
- morning stiffness - for at least 1hr
- swelling in 3+ joints
- swelling of wrist, metocarpophalangeal or proximal interphalangeal joints
- symmetric joint swelling
Hand X-ray changes:
- erosions or bony decalcification
- rheumatoid subcutaneous nodules
Serology:
- RF or anti-citrullinated peptide/protein Abs
- elevated acute phase reactants (ESR/CRP)
Pattern of joint involvement in RA
Affects small distal joints first before moving on to affect others
- wrist - 80%
- Metatarso-phalangeal - 90%
- metacarpo-phalangeal/proximal interphalangeal - 90%
Does axial skeleton tend to be involved with RA?
no
Pathohistology of RA - synovial inflammation & differentiation
- complex inflammatory inflitrate & abnormal differentation of synovium (pannus)
- angiogenesis –> cellular infiltrate –> cytokine secretion –> T & B cell activation –> tissue oedema & fibrin
Extra-articular manifestations of RA
- Rheumatoid nodules - subcutaneously on extensor surfaces
- Lung disease - pleural effusion, pneumonitis, intersitital lung disease, nodules
- Pericarditis
- Vasculitis - cutaneous (digital infarction), peripheral nerves (vasa nervora)
- Neutropenia + splenomegaly (Fetty’s syndrome)
- Eyes - scleritis, episcleritis
Discuss features of Rheumatoid Factor for RA
- Ab to Fc portion of IgG
- not specific for RA (b/c RF present in IgG, IgM & IgA)
- IgM RF correlates best with disease activity & severity (including extra-articular manifestations)
Discuss features of Anti-Cyclic Citrullinated Peptide Ab for RA
- more specific for RA but not more sensitive (compared to RF)
- citrulline = modified version of a.a. arginine
- Citrullination = more common in RA
Which is a more specific &/or sensitive Ab for RA?
RF = more sensitive
Anti-CCP = more specific
What genome is involved in RA?
HLADRB1
What is Seronegative Arthritides?
inflammatory arthridites NOT associated with RF
Examples of Seronegative Arthridites
PAIR
- Psoriatic arthritis
- Ankylosing spondylitis
- arthritis associated with IBD
- reactive arthritis
Seronegative arthritides are more common in males or females?
Males
Clinical manifestations of Seronegative arthritides (x6)
starts in early adulthood
- sacroiliac joints & axial skeleton
- sacroilitis
- ascending inflammation of spine
- enthesitis (inflammation of tendon, ligament or joint capsule insertions)
- dactylitis (inflammation of entire digit)
- limb joints
What is Ankylosing Spondylitis?
chronic inflammatory disease of spine & sacroiliac joints
Psoriatic arthritis
Joint pain & stiffness associated with psoriasis
IBD
Crohn’s disease or UC often accompanied by ankylosing spondylitis or peripheral arthritis
Reactive arthritis
Classic triad of symptoms:
- conjunctivitis
- urethritis
- arthritis
‘cant see, can’t pee, can’t bend my knee’
Extra-articular manifestations of Seronegative arthridites (x5)
- iritis (anterior uveitis)
- enteritis
- urethritis
- skin disease
- aortitis & conduction defects
…………. polymorphism has an association with seronegative arthritides
HLA-B27
HLA-B27 & pathogenesis
misfolded HLA-B27 accumulates in ER triggering an unfolded protein response (pro-infammatory)
Other polymorphism associated with Seronegative arthridities
abnormality in IL-17 production due to hyper-responsivness to IL-23 by NK or gamma/delta T cells
Systemic Lupus Erythematosus
complex autoimmune disease with various clinical manifestations & complex pathogenesis
- more severe in Africans & Asians
- F:M = 9:1 - most marked in child-bearing years
Pathology of SLE
inflammation with auto-Ab deposition in end-organs
Key auto-Ags for SLE
- chromatin
- ribonucleases
- phospholipids
Key findings of auto-Abs in SLE
- dsDNA Ab titre (not ANA) - reflects disease activity
- Hypo-complementaemia with disease activity
- defective acute phase response - CRP
Characteristics of auto-Ab response in SLE
- high affinity, somatically mutated Abs (products of T-dependent & B cell responses, arising from GC reactions)
- produced form long-lived plasma cells in BM
- aberrant T cell help - B cell priming, centrocyte rescue in GC
Clinical manifestations of SLE
RASH OR PAIN
- Rash
- Arthritis
- Soft tissues/serositis
- Hematological disorders
- Oral ulcers
- Renal disease
- Photosensitive , postive VDRL/RPR
- Antinuclear antibodies
- Immunosuppressanta
- Neurologic disorders
Relationship between apoptosis and lupus autoantigens
- accumulation of auto-Ag on blebs of apoptotic cells
- provide eat me singals to ensure efficient phagocytosis of apoptotic cells (actively anti-inflammatory)
- impaired phagocytosis of apoptotic cells by monocytes from C1q-deficient pts
- corrected by addition of C1q
4 types of Juvenile Idiopathic Arthritis - compare/contrast clinical, lab, complications & pathogenesis where possible in a table
- Systemic
- Enthesitis-related
- Seropositive
- Oligoarthritis
