Inflammatory arthritis Flashcards
What are the main characteristics of inflammatory arthritis?
- Heat/ Warmth
- Redness/ Erythema
- Pain
- Swelling
- Morning stiffness - usually gets better after a while
- Systemic symptoms (malaise, wt loss, fever etc.)
Why is it important to differentiate between inflammatory and non - inflammatory types?
- Inflammatory is potentially more serious
- Many inflammatory arthritis have systemic manifestations
- Early recognition and intervention improves outcome
What are some causes of acute/ self limiting inflammatory arthritis?
- Infections e.g Parovirus B19 or Streptococcus, mycoplasma
Name some chronic inflammatory arthritis
- Rheumatoid arthritis
- Spondyloarthropathies e.g Psoriatic arthritis and Axial SpA
- Crystal arthritis
- Connective tissue disease (SLE, Scleroderma)
What is the history/examination of inflammatory arthritis?
- Age
- Sex
- Mode of onset
- Severity of joint inflammation (intensity, number of swollen joints)
- Temporal pattern of joint involvement
- Distribution of joint involvement
What are the laboratory investigations in polyarthritis?
- FBC
- ESR or CRP
- RF, ANA, anti- CCP, HLAB27
- Uric acid
- Synovial fluid analysis
What does sclerosis mean?
Subchondral bone formation due to loss on cartilage - shows increased bone density on radiographs
What are radiographical erosions?
Bone destruction
What are some causes of polyarticular pain?
- Hyper & Hypothyroidism
- Hyperparathyroidism
- Multiple sclerosis (malignancy)
- Chronic Pain syndromes (Fibromyalgia)
What is the Norfolk arthritis register (NOAR)
A register of patients who are over the age of 16 and present with 2 or more swollen joint. Their Sympotms usually lasts for 4+ weeks
What are the aims of NOAR?
- Identify risks factors for the development of IP (inflammatory polyarthritis) and RA
- To establish the incidence of IP and RA
- To identify predictors of outcome in IP and RA
- To measure the burden of illness
Rheumatoid arthritis is (asymmetrical/symmetrical) and affects ….. of hands and feet
- Symmetrical
2. Small joints
What is the clinical presentation of RA?
- Insidious (70%)
- Additive - starts with one joint then expands to others
- Small joint involvement (MCP, PIP, MTP, and wrist)
- Uveitis, Rheumatoid nodules
- Could me palindromic, polymyalgia
What are the classification criteria for RA?
- Morning stifness lasting more than 1 hour
- Arthritis is more that 3 joints for 6 weeks
- Hand involvement for 6 weeks
- Symmetry
- Nodules
- Radiographic erosions
- Positive rheumatoid facor
What is the rheumatoid factor made up of?
An IgG + Anti-IgG (IgM) component
What happens after IgG and IgM bind in RA?
- Complement is activated2. 2. Inflammatory cytokines released
- They damage cartilage, destroy bone and produce inflammation
In what other conditions is rheumatoid factor also found in?
- Sjogren’s Syndrome
- SLE
- JIA
- Hepatitis
- TB
- Chronic bronchitis
- Normal finding in older people
What predicts RA?
Anti - CCP (anti-cyclic citrullinated peptide) - autoantibody that works against normal antibodies.
What predicts RA?
Anti - CCP (anti-cyclic citrullinated peptide) - levels can reflect response to treatment
Where are citrullinated proteins found on?
In the inflamed synovium
How common are erosions in RA?
40-73% of patients develop X-ray erosions within the first year
Males are more likely to develop RA? True or False
FALSE
- Women are more affected
What is the overall prevalence of RA?
0.8 - 1 %
What are some risk factors of RA?
- Smoking
- Obesity
- Immunisation
- Blood transfusion
- Previous termination of pregnancy
Vitamin C and Vitamin E can be effective in preventing RA? True or False
TRUE
The prevalence of RA is high in Pima Indians. What is the percentage
5 -6%
RA is more common in ages above 30? True or False
TRUE
What are the treatments given to RA patients and in what cases are they administered?
Mild - NSAIDs
Moderate - DMARDs
Severe - Combination therapy (steroids)
Very severe - Biological therapy
How is the disease activity measured?
Through the disease activity score ( 28 joints are assessed)
- tender joint score
- swollen joint score
- ESR levels
- General Health assessment
(patient tells us how active they think their disease is)
Name 3 DMARDs
- Salazopyrine
- Hydroxychloroquine
- Leflunomide
- Methotrexate
What are some predictors of a poor prognosis?
- RF positive
- Anti - CCP positive
- Rheumatoid nodules
- HAQ score
- Poor grip strength
- High number of swollen joints
What do biologic agents for RA include?
- Anti - TNF
- Rituximab
- Abatacept
- JAK inhibitors (high cost drugs)
- Tocilizumab
When can patients be administered biological agents for RA?
When they didn’t respond to 2 or more DMARDs including methotrexate
What are some surgical treatments for RA?
- Arthroplasty
- Repair of tendon rupture
- Synovectomy (rarely done now - tissue surrounding a joint is removed)
Why is it important to treat RA early?
- reduces risk of long - term outcomes
- could lead to complete loss of mobility
- could lead to bone destruction
- could have other systematic effects
What is enteropathic arthritis?
- HLA B27 athropathy
- behaves like AS
- associated with Crohn’s disease and spondylitis (inflammatory bowels disease)
In enteropathic arthritis, the arthritis and gut symptoms are usually linked. True or False
TRUE
Where does enteropathic arthritis usually present?
Asymmetrical large joints
- also some dactylitis and uveitis
How many people in the population are affected by psoriasis?
1-3% of patients
What is the prevalence of psoriasis and does it affect males and females equally?
- 0.67%
- Yes, it affected males and females equally
Nail lesions/ nail pitting is a very common way to predict psoriatic arthritis. True or false
TRUE
What are the main presentations of psoriatic arthritis?
- usually asymmetrical
- DIP joint involvement usually
- Rash (usually vesicular)
What are the main treatment types for psoriatic arthritis?
- NSAIDs
- DMARDs
- Biological therapy
- JAX Inhibitors
- Physio and Education
When can a person be administered biologics?
- if they have 3 or more tender & 3 or more swollen joints
- if they haven’t responded to 2 DMARDs
What is enthesitis?
Inflammation at the point where a tendon or ligament insert into the bone
What are some radiographic changes seen in psoriatic arthritis?
Pencil in cup deformity
In Axial spondylitis where does the inflammation start?
- In the sacroiliac joints and then it moves up the spine
What is the clinical criteria for diagnosis AS?
- Low back pain and stiffness for more than 3 months (improves with exercise)
- Limitation of motion of the lumbar spine in both the sagittal and frontal planes
- Limitation of chest expansion
What are some radiographic features of AS?
- Bone marrow edema (swelling caused by fluid)
- Sacroiliitis with pain and stiffness + new bone formation
Ankylosing spondylitis is the term given to patients who have inflammation of specifically the SIJ first. TRUE or FALSE
TRUE
- usually patients with ankylosing present with radiographic disease and spinal changes
Axial Spondylitis is the term given to patients who have general inflammation of the spine. TRUE or FALSE
TRUE
Name some clinical features of AS
- Gradual onset
- Early morning stiffness
- Improves with movement
- Usually starts at a younger age
- Responds well to NSAIDs
Name some treatments for AS
- Physiotherapy
- NSAIDs, biologics
- DMARDs for peripheral joints only
- Monitoring of disease activity
All AS patients have a radiographic disease. True or False
FALSE
- not all AS patients present with spinal changes
What are some other systematic symptoms associated with SpA?
- uveitis
- anemia
- Weight loss
- Psoriasis
- inflammatory back pain
- Crohn’s disease
- Dactylitis
- Enthesitis
- Osteoporosis
What investigations are used to diagnose AS?
- FBC, ESR AND CRP
- X -Ray SIJ, Spine
- MRI
What is the definition of reactive arthritis?
A sterile joint inflammation that develops after a distant infection
What are some triggering infections of ReA?
- Throat
- Urogenital (chlamydia, Neisseria)
- GI tracts (salmonella, shigella etc.)
- Meningococci, streptococci
Females are more affected by ReA than men. TRUE OR FALSE
FALSE
Males and females are equally affected.
What age group is usually affected by ReA?
Young adults aged 20 - 40
Is the HLA B27 gene involved in reactive arthritis?
Yes it is, reactive arthritis tends to be more severe if HLA B27+
What is the first line management in treating ReA?
Test for septic arthritis first!!
- aspirate joint
What are some clinical features of ReA?
- history of infection up to 2 weeks before
- family history
Name 3 systemic symptoms of ReA
- Malaise
- Fatigue
- Fever
Reactive arthritis usually affects larger joints and is asymmetrical - true or false
true
What should you look out for when examining patients with reactive arthritis
- Redness/ erythema
- Swelling
- Temperature (warmth)
State 3 extra- articular msk manifestations associated with ReA
- Tenosynovitis - (inflammation of tendon sheath)
- Enthesopathy
- Plantar Fasciitis (pain at bottom of foot)
What investigations should you take for ReA?
- gram stain
- polarised light microscopy
- culture from (faeces, urine, throat, blood/serology)
- X-rays
- autoantibody screen
How is reactive arthritis managed?
- Analgesia
- NSAIDs
- Steroids
- Antibiotics (if infection is still present)
- Splinting
State some prognosis of ReA
- self - limiting in weeks
- some back pain
- Arthralgia
- Synovitis
- usually good prognosis
What are the main triggers for inflammation?
- Infections
- Tissue necrosis
- Foreign bodies
- Immune reactions
What are some features of acute inflammation?
- Immediate response
- Non specific (innate immunity)
- Edema and neutrophils in tissue
Inflammatory cells allow plasma proteins and fluid to exit blood vessels and to enter interstitial space. TRUE or FALSE
TRUE
What is a virulence factor?
- trigger acute inflammation
- molecules that help pathogens to colonize tissues and cause infection
What are PAMPS? (Pathogen associated molecular patterns)
- trigger acute inflammation
- small molecules with conserved patterns that are shared across many different pathogens
What are DAMPS? (Damage associated molecular patterns)
- intercellular proteins released when a cells plasma membrane is injured or a cell dies - trigger inflammation too
What are DAMPS and PAMPS recognized by?
Pattern recognition receptors
- cell surface receptors on various leukocytes
- begin inflammatory response
What is the function of IL-1?
Recruitment of leukocytes
What are the 5 steps of inflammation?
- Recognition of injurious agent
- Recruitment of leucocytes
- Removal of the agent
- Regulation of the response
- Resolution
What is the role of cytokines?
Proteins that are secreted my main dendritic cells, activated lymphocytes and macrophages
- regulate immune reaction
s (orthokrene, parakrene and
Name 5 mediators of acute inflammation
- Hageman factor
- Complement system
- Mast cells
- Arachidonic acid metabolites
- Toll - like receptors
What is the Hageman factor (Factor 12)
- It is a clotting factor
- triggers fibrin formation through activation of Factor 11
What is the intrinsic clotting pathway activated by?
The Hageman factor
Where is the Factor 12 produce?
Liver
How is the hageman factor activated?
By contact (coming into contact with pathogens/microbes/ yeast/ parasites) OR coming into contact with glass and medical apparatus
What is the function of anaphylatoxins? (C3a, C4a, C5a)
- causes histamine to be released from mast cells
- C5a is a chemotactic and activation agent for neutrophils, monocytes, eosinophils and basophils
What is the function of histamine
Histamine is involved in the inflammatory response and has a central role as a mediator of itching.
What is the function of histamine
Histamine increases the permeability of the capillaries to white blood cells and some proteins = more accessibility to pathogens
C5b, C6, C7, C8 and C9 (membrane attack complex) flood the cell with water and ions which causes lysis. TRUE or FALSE
TRUE
Why are mast cells important in inflammation?
Because they’re membranes contain pre-made granules that can be immediately released = immediate reaction
Where are mast cells found?
- distributed throughout connective tissues
How are mast cells activated?
- complement proteins (C3, C5a)
- tissue trauma
- cross linking of cell surface IgE by antigen
What happens when a mast cell becomes activated?
- granules are released
- vasodilation of arterioles - increased vascular permeability
Where are arachidonic acid metabolites derived from?
Membrane phospholipids
What is prostaglandin E2 responsible for?
Pain and Fever
What is prostaglandins, IL- 1 and TNF responsible for?
Fever
Where are leukotrienes produced and what is their function?
- vasoconstriction
- bronchospasm
- vascular permeability
Where are leukotrienes produced and what is their function? (LTC4, LTD4, LTE4)
- vasoconstriction
- bronchospasm
- vascular permeability
What is LTB4 responsible for?
Neutrophil attraction and activation
Steroids are not anti - inflammatory agents. TRUE OR FALSE
FALSE
Where are toll - like receptors found?
On the cells of innate immune cells e.g macrophages and dendritic cells
- on some adaptive immunity cells e.g lymphocytes
What are toll like receptors activated by?
- PAMPS
What do granules do?
They contain enzymes that break down pathogens and reduce inflammation
What is acute cellulites caused by?
Bacterial infection
What does
- Rubor
- Calor
- Dolor
- Tumor
- Functio Laesa
- Rubor - redness
- Calor - heat
- Dolor - pain
- Tumor - swelling
- Functio laesa - loss of function
What causes rubor and color?
- vasodilation causing increased blood flow
- this is due to the relaxation of arteriolar smooth muscle
Why do patients get pyrexia related to inflammation?
- pyrogens (proteins from gram - negative bacteria) cause macrophages to release IL -1 and TNF = increases COX activity in the hypothalamus
- COX produces prostaglandins = temperature raised
What is swelling caused by?
- leakage of fluid from post - capillary venules into interstitial space (exudate)
What inflammatory mediators cause pain?
- bradykinin and PGE2 sensitise sensory nerve endings
What cells arrive first during inflammation?
Neutrophils
State 3 roles of neutrophils
- Margination (cells marinate from centre of flow to the periphery of the venule)
- Rolling - neutrophils roll along the endothelial surface
- Adhesion - neutrophils adhere to the walls of the endothelium to move through them with the help of integrins
- Transmigration and chemotaxis
- Phagocytosis
- Destruction of pathogens
- Resolution
What are integrins
Integrins are the principal receptors used by animal cells to bind to the extracellular matrix.
Name 2 outcomes of inflammation
- resolution and healing
- abscesses formation
When do macrophages peak?
2-3 days after inflammation begins
What is the role of macrophages?
Phagocytosis
Rheumatoid arthritis is managed by the MDT and methotrexate is an MDT drug. TRUE OR FALSE
TRUE
What are the effects of bradykinin?
- Vasodilation
- Increased vascular permeability
- Pain
Name 3 causes of chronic inflammation
- Persistent infection ( e.g myobacteria, parasites and fungi)
- Autoimmune disease
- Foreign material
- Carcinoma
What are the main inflammatory cells
- Macrophages
- Lymphocytes
- Plasma cells
What is the dominant cell in most chronic inflammatory reactions?
Macrophages
Where are macrophages derived from
- haematopoietic stem cells and circulate as monocytes
Where are monocytes found in?
- connective tissue
- liver (kupffer cells)
- spleen
- lymph nodes (sinus histocytes)
- central nervous system
The half-life of monocytes is about a day whereas the lifespan of tissue macrophages is several months or years. TRUE OR FALSE
TRUE
Where are T-lymphocytes produced?
Bone marrow as progenitor T-cells but further developed in the THYMUS
TCR complex does not recognise antigen presented on MHC molecules. TRUE OR FALSE
FALSE - IT DOES
Where are B - lymphocytes produced
Bone marrow
After immunoglobulin gene rearrangement what do B-lymphocytes turn into?
Naive B-Cells that express IgM and IgD
What do antigens bind to that cause maturation of plasma cells
IgM or IgD
What type of protein are IgM or IgD?
Antibodies
What are the characteristics of plasma cells seen under a microscope?
- oval shape
- larger than neutrophils and rbc
What is granulomatous inflammation?
Inflammation that deals with tricky pathogens
Associated with foreign material, Crohn’s disease or Cat scratch disease, sarcoidosis
Define granuloma
Collection of activated macrophages/epithelioid histocytes
What are epithelioid histocytes
Macrophages that resemble epithelial cells
Granulomas can be non caseating or caseating. What does that mean?
Non - caseating: Non- necrotizing granulomas
Caseating - necrosis involving dead cells with no nuclei and debris (cheese like necrosis)
What is sarcoidosis?
- abnormal collection of granulomas usually in the lungs, skin or lymph nodes
What is the early stage of wound healing?
- transition from acute inflammation
The inflammatory phase of healing includes
coagulation - platelets cells , neutrophils and macrophages
What is the function of platelets during wound healing?
- Clot formation
- As they degranulate they release growth factors that initiate proliferation of undamaged cells
When does healing start?
When inflammation begins occurs via regeneration and repair
What does the ability to regenerative depend on?
depends on the regenerative capacity of the cell
What are the three types tissues can be divided into based on regenerative capacity?
- Labile - have stem cells that continuously cycle to regenerate tissue
- Stable - cells are usually inactive but can re -enter the cell cycle to regenerate tissue when necessary
- Permanent - lack of significant regenerative potential (e.g skeletal muscle)
Define repair
Replacement of damaged tissue with a fibrous scar - occurs when regenerative cells are lost e.g deep skin cut
Granulation tissue formation is the second phase of repair. TRUE OR FALSE
FALSE - It is the initial phase
What does granulation tissue comprise of?
Proliferated capillaries providing nutrient, fibroblasts and myofibroblasts (cause wound contraction)
What is regeneration and repair mediated by?
- Paracrine signalling by growth factors (macrophages secrete growth factors)
Interaction of growth factors with receptors results in …..(1)……. and ……..(2)
- Gene expression
2. Cellular growth
What are the functions of transforming growth factor -beta?
Fibroblasts growth and inhibition of inflammation
What mediator causes growth of endothelium, smooth muscle and fibroblasts?
- Platelet derived growth factor
What is angiogenesis?
When new blood vessels form from pre-existing vessels
What are the 4 phases of wound healing
- Coagulation phase (involves neutrophils etc.)
- Inflammatory phase
- Proliferative/granulation tissue phase
- Remodelling phase (myofibroblasts begin to remodel extracellular matrix)
What are growth factors needed for?
Recruitment of epithelial cells
What happens during primary intention of wound healing?
- wound edges brought together - leads to minimal scarring
What happens during the secondary intention of wound healing?
- edges are not brought together
- granulation tissue fills the gap
- myofibroblasts contract the wound
> scar forms
What is the difference between a hypertrophic and keloid scar?
Hypertrophic - excess scar production local to wound
Keloid - excess scar production that is larger than wound
Name 3 factors that can delay healing
- Vitamin C deficiency
- Copper deficiency
- Zinc deficiency
- Foreign bodies
- Ischaemia
- Diabetes
- Malnutrition
What causes hypersensitivity reactions?
- Autoimmune diseases
- Reactions against environmental antigens
- Reactions against microbes
What is lyme disease?
A bacterial infection that can be spread to humans by infected ticks
What are the clinical features of lyme disease
- skin reaction: erythema migrans (rash)(looks like a bulls eye)
- Peripheral neuropathy (nerve damage outside cns)
- Lymphocytic meningitis
- Cranial nerve palsies (loss of function of cranial nerve)
- Late disease: arthritis affecting larger joints
How do you diagnose lyme disease?
- mostly clinical
- antibody detection is frequently negative
- Immunofluorescence or ELISA can give false positive reaction for many other conditions
How do you manage lyme disease
Medication
- doxycyline
- amoxicillin
for minimum 28 days
How can you prevent lyme disease?
- protective clothing
- insect repellents in tick-infested areas
What are the seronegative features of RA?
- IBD
- Uveitis
- Psoriasis
- Spinal symptoms
