Inflammatory Conditions Flashcards
what are the key differences between the innate and adaptive immune response?
-innate is non specific whereas adaptive is specific
-innate is rapid response whereas adaptive is slower to respond
-innate has no memory whereas adaptive recognises previous pathogens
-innate limits and contains infection until adaptive system is ready whereas adaptive takes over from innate system to eradicate the pathogen
what does the ‘first line of defence’ consist of?
physical and mechanical barriers
give some physical barriers
-keratinised stratified squamous epithelium - skin epidermis which sheds so helps to remove microorganisms
-mucous membranes line the body cavities, digestive and respiratory tracts- mucous is sticky so helps trap debris and microbes
-hair traps large particles
-cilia moves mucus and dust particles
give examples of mechanical barriers
coughing, sneezing and swallowing to remove mucus
give 3 innate immune responses
inflammation
complement cascade
cells of innate immunity
give examples of acute and chronic inflammation?
-cuts
-bruises
-sports injury
-simple infections like flu
what are the 4 cardinal signs of infection?
redness
heat
swelling
pain
what are the main aims of inflammation?
-attempt to dispose of pathogen, toxin/ foreign material at the site
-prevent spread of pathogens
-prepare site for tissue repair or wound healing
what are the main stages of the actue inflammatory reaction?
- Tissue injury or pathogens activate
mast cells resident in tissues - Activated mast cells produces
histamine, which causes blood
vessels to dilate (vasodilation) and
increased capillary permeability,
resulting in - Leakage of blood plasma
containing proinflammatory
proteins (cytokines / chemokines) - Further activation of resident cells
and release of cytokines - Emigration of phagocytes
Initiation of clotting mechanism
along with tissue repair
give some diseases due to chronic inflammation
-rheumatoid arthritis
-psoriasis
-inflammatory bowel diseases
what is an allergy?
an inflammatory response against a specific allergen or antigen which can range from minor irritation to anaphylaxis
where can allergic reactions cause inflammation
skin, sinuses, airways, digestive system or conjunctiva
what immune response is the complement system part of?
innate immune systenm
what 3 ways does the complement system destroy microbes?
-inflammation
-opsoisation
-cystolysis
where does complement system come from?
plasma proteins produced in liver that circulate in the blood
What are the two types of leukocytes?
-polymorphonuclear granulocytes
-mononuclear agranulocytes
give the three Polymorphonuclear granulocytes and what they do
-neutrophils: mobile phagocytic specialists, first in bacterial infection, scavenge to clean up debris
-eosinophils: increase in allergic conditions e.g. parasitic infection
-basophils: synthesise, store and release histamine and heparin
give the two mononuclear agranulocytes and what they each do
-phagocytes, last 1-2 days in blood and months - years in tissue as large mature macrophages
- lymphocytes which consist of B cells that make plasma cells and antibodies and then T cells which are part of cell mediated immunity
what are the functions of leukocytes?
- Defence against invading
pathogens - Remove cellular debris
- ‘Immune surveillance’:
identifying and destroying
abnormal cells (e.g. cancer)
what happens to B cells before they reach the lymphatic system compared to t cells?
B cells mature in the red bone marrow and then travel to various sites in the lymphatic system whereas T cells develop in the bone marrow, travel to the thymus and then mature before being released into the lymphatic system
what are the 5 types if antibodies?
gA, IgD, IgE, IgG,
IgM
what are the 5 functions of antibodies?
-agglutination/aggregation on target surface
-Mark cells for destruction by
complement system (opsonisation)
-Activate complement system
-Enhance phagocytosis
-Stimulate natural killer cells
what are the different types of T cells?
-cytotoxic T cells
-Helper T cells
-T memory cells
-Regulatory T cells (less common as they limits extent of immune response)
what do cytotoxic T cells do?
1.bind with target cell
2. release perforin
3. create pores in cell membrane triggering lysis
4. release granzymes which are like digestive enzymes which trigger destruction of the cell
what are 5 functions of helper T cells?
*Increase antibody function
*Increase action of cytotoxic T cells
*Chemotaxis (neutrophils & monocytes)
*Macrophage inhibition factor
*Activates eosinophils
what is the uvea?
middle layer of the eye between sclera and retina consisting of iris cilliary body, choroid and rpe
what are the different types of uveitis and what do they consist of?
- Anterior Uveitis = Anterior chamber
- Intermediate = vitreous and plan plana
- Posterior = Retina, choroid
- Panuveitis = entire uveal tract
what are the three causes of uveitis?
-infection
-autoimmune
-masquerade = underlying disease like malignancy
what % of intermediate uveitis cases are idiopathic?
50%
what are the symptoms of intermediate uveitis?
- Blurred vision
- Floaters
- Normally painless
- No redness
how can you classify intermediate uveitis?
using SUN classification (check ss)
what are the signs of intermediate uveitis?
- VA – dependant on severity and presence of CMO
- May have spill over inflammation in AC
- Vitreous cells
- Vitreous haze and condensation
- Snowballs – whote focal collectionsof inflammatory cells and
exudate - Snowbanking – peripheral fibrovascular plaque
- Peripheral periphelbitis – mild peripheral vascular sheathing
- CMO occurs in up to 50%
what conditions can be secondary to intermediate uveitis?
-cataract
-secondary glaucoma
what are causes of intermediate uveitis?
- 50% idiopathic / undifferentiated
- Multiple sclerosis
- Sarcoidosis
- Lyme disease
- Syphilis
- TB
give 3 masquerade causes of intermediate uveitis
- Lymphoma
- Endophthalmitis
- toxoplasmosis
what is the posterior pole?
the space of the retina between the optic disk and the macula
what imaging would you do for a suspected naevus?
- OCT to show reassuring lack of
features - Auto fluorescence may show subtle
changes which could be suspicious - Ultrasound
what are the review guidelines of a neauvus?
-No suspicious features – 6 months until stability established – normally 1 year then annual review - Optometry
-1 or 2 suspicious features every 4-6 months – Secondary care
-3 or more suspicious features refer for ocular oncology assessment – Tertiary care
what is the most common intraocular malignancy?
melanoma
look at ss to see how to help remember melanoma signs
ok
what is a choroidal haemangioma?
A mass of varying sized vascular channels
within the choroid
* May cause exudative detachment
what are the signs of choroidal haemangioma?
- An oval orange mass with indistinct
margins - Sub retinal fluid may cause symptoms
- ICG shows strongly hyperfluresent
vessels
what are vasoproliferative tumours secondary to?
uveitis, trauma, retinal
dystrophies
what are the treatments for vasoproliferative tumours?
- Cryotherapy or brachytherapy
- May induce regression
- Prognosis poor if macular involvement
name ocular tumours associated with the choroid and sclera
- naevus
- melanoma
- Choriodal haemangioma
- melanocytoma
- osteoma
- Metastatic disease
name ocular tumours associated with the neural retina
-retinoblastoma
-retinal astrocytoma
-tuberous scerosis
name ocular tumours associated with retinal vasculature
- Capillary haemangioma
- Caverous haemangioma
- Racemose haemangioma
- Vasoproliferative tumour
name ocular tumours associated with the RPE
- CHRPE (Congenital
hypertrophy of the RPE) - Combined harmatoma of retina and RPE
- Congential simple hamartoma of the RPE
- Adenoma nd adenocarcinoma of the RPE
What is the main systemic cause of uveitis?
autoimmune disease
what is autoimmune disease?
-the abnormal response of the body in absence of normal inflammatory stimuli which attacks normal healthy tissue, often has a genetic predisposition but can be idiopathic
give 3 anterior eye diseases
-episcleritis
-scleritis
-anterior uveitis
what is episcleritis?
inflammation of the episcleral, normally idiopathic but may have systemic associations (same as scleritis)
what are the symptoms of episcleritis?
-mild aching/ burning sensation
-may be tender to touch
-epiphora (excess tears/wateriness) is common
-may be recurrent
what are the signs of episcleritis?
-sectoral/ diffuse redness
-dilated episcleral vessels which may blanch w/ phenylephrine
-no corneal or anterior chamber activity
-VA unaffected
how do you manage episcleritis?
-usually self resolving
-cold compress
-use NSAID like ibuprofen which may help if the patient can take them
-in non resolving cases can consider topical steroids
why is it better not to give steroids for episcleritis?
as the inflammation often rebounds when you stop using the steroids
what is scleritis?
inflammation of the sclera that can be bilateral and is sight threatening
what types of scleritis can you get?
-either anterior (90%) or posterior
-anterior types include diffuse, nodular and necrotising
what are the causes of scleritis?
-can be idiopathic
-autoimmune disease (as in 30-40% of cases)
-infection
what autoimmune diseases can cause scleritis?
-RA
-systemic lupus erythematous (SLE)
-sarcoidosis
what infections can cause scleritis?
-HZO
-pseudomonas
-fungal infection
-TB
-syphilis
what are the symptoms of scleritis?
-extreme pain
-pain may be made worse by eye movement
-likely to disturb sleep
-photophobia
-reduced VA
what are the management options for scleritis?
Urgent referral into HES - additional risks come with treatment
Need oral anti inflammatory treatment
-less severe cases may respond to NSAID
-often needs oral steroids which require systemic checks
what are the signs of scleritis?
-hyperaemia of superficial and deep scleral vessels
-Does not blanch with phenylephrine
-Anterior chamber inflammation may be present
-Corneal infiltrates may be present
-May cause scleral thinning which remains after resolution
-Entire eye very tender to touch
-Posterior inflammation only visible using ultrasound
what can cause anterior chamber inflammation?
-idiopathic
-autoimmune disease
-infections
-uveitis syndromes like Fuchs heterochromic iridocyclitis
-trauma
what are the symptoms of anterior chamber inflammation?
- Dull ache, pupil constriction makes it worse
- Photophobia
- Redness
- Mildly reduced VA
- Epiphora
what are the signs of anterior chamber inflammation?
*hyperaemia
*cells floating in the anterior chamber (flare)
*posterior synechiae
*increased IOP due to flare blocking trabecular meshwork
how can you manage anterior chamber inflammtion?
- Posterior segment check essential to exclude intermediate or posterior involvement
- Exclude possible infectious cause
- Topical steroid – frequency dependant on severity – up to hourly for 3 days, then taper
over a minimum period of 6 weeks - Cycloplegia in acute phase – acts as pain relief
- Recurrent or bilateral episodes require Ophthalmologist review to exclude other causes
- First episode in older adult (60+) unlikely to idiopathic so requires referral to
Ophthalmology to exclude masquerade (e.g. syphilis, lymphoma)
what are the causes for intermediate uveitis?
- Idiopathic (undifferentiated) – 70% of cases
- Auto-immune e.g. Sarcoidosis, Inflammatory bowel disease
- Infectious
- Systemic disease e.g. Lymphoma, MS
how can you manage intermediate uveitis?
- Always requires referral to secondary care as an urgent
- Full systemic history
- Full ocular examination
- Systemic investigations including blood tests, chest x-ray etc
- Oral steroid most common management
- May require other immunosuppression therapy
- May be managed by steroid inplant (Ozurdex / Iluvien)
what are the symptoms of posterior uveitis?
- Painless loss of vision
- Blurring
- Floaters
- photopsia
what are the signs of posterior uveitis?
- Mild vitritis
- Posterior pole lesions
- Ill defined patches – may be white / creamy /grey depending on cause
- Peripheral vasculature shutdown
- Neovascular changes
- CNV
give examples of inflammation of the posterior pole
-retinitis
-choroiditis
-chorioretinitis
what are the causes of posterior inflammation?
- Idiopathic (rare)
- White dot syndromes (no systemic associations)
- Auto-immune e.g. Sarcoidosis, Bechets
- Infectious e.g. Cytomegalovirus (CMV) Acute retinal necrosis (Herpetic)
- Systemic associations e.g. Lymphoma
what is choroiditis?
inflammation of the choroid w/ inflammatory foci at the level of the choroid and rpe and isolated choroiditis is rare
what is retinitis? what are the signs?
-inflammation of the retina usually in conjunction with choroiditis and vasculitis
-demarcated areas of inflammation, pigmented atrophic areas when no longer active and haemorrhage and exudates are often apparent
what is vaculitis? what are the signs?
inflammation of the retinal vasculature - usually not isolated
-perivascular sheathing
-exudates
-cotton wool spots
-occlusion
-neovascular changes
what is neuroretinitis and give some signs
-inflammation of the optic nerve, peripapillary area and the neuro retina
-lipid rich exudates may form macula star and may clinically be similar to hypertensive retinopathy
give to parasitic retinal infections
toxoplasmosis(may be asymptomatic) and toxocara
give three viral retinal infections
- Acute retinal necrosis
(ARN) – Herpes simplex
(HSV)/ zoster (HZV) - Progressive retinal necrosis
PRN also known as (poster or
progressive outer retinal
necrosis or PORN) - HZV
-cmv retinitis (immunocompromised patients)
give two fungal retinal infections
-candida
-Presumed ocular histoplasmosis syndrome (POHS) – seen in HIV
give three bacterial infections that can cause retinal inflammation
-tb
-syphyllis
-lyme disease
give 6 autoimmune diseases that can cause inflammation to the eye
- Multiple Sclerosis
- Sarcoidosis
- VKH
- Bechets
- Miscellaneous Idiopathic chorioretiopathies
- Sympathetic Ophthalmia
what is sarcoidosis?
an autoimmune disease where collections of inflammatory cells create granulomas which can occur throughout the body
what are the signs of sarcoidosis?
- Chest xray shows hilar lymphadenopathy
- Bloods show a raised serum ACE
give an ocular complication of sarcoidosis
-intermediate and posterior uveitis
-granulomatous anterior uveitis
what is bechets disease? what are some symptoms?
-idiopathic multisystem disease that causes vasculitis to be always present.
-Recurrent mouth ulcers, genital ulceration and uveitis
-causes inflammation throughout entire uveal tract
what is the prevalence of a naevus in caucasians?
5-10% with growth occuring around puberty
what are the signs of a nauvus?
- Slate grey lesion with feathery
margins - Overlying drusen are typical and
reassuring - Depigmented halo is common
- No associated sub retinal fluid
what is the most common intraocular malignancy?
melanoma
for melanoma:
-when is peak presentation?
-what is its histology
-where is metastasis common?
-what is mortality like?
- Peak presentation 60 years
- Histologically spindle or epithelioid
cells present - Metastasis is commonly to the liver,
bone and lung but only 1-2% have
detectable mets at presentation - Mortality is up to 50% at 10 years
what are the signs of melanoma?
- Commonly penetrate bruchs and
RPE with herniation into the sub
retinal space – Collar stud
appearance - Solitary elevated sub retinal grey-
brown mass - Can be amelanotic
- 60% are located within 3mm of the
optic disc - Clumps of lipofuscin (orange pigment
overlying is common) - Associated haemorrhage, and sub
retinal fluid is common
how can you categorise retinal lesions?
moles score - check ss
what are the review guidlines for a retinal growth?
No suspicious features – 6 months until stability established – normally 1 year then annual review - Optometry
One or two suspicious features every 4-6 months – Secondary care
3 or more suspicious features refer for ocular oncology assessment – Tertiary care
give examples of anti inflammatory drug types
-corticosteroids
-non-steroidal anti-inflammatory drugs (NSAIDs)
give examples of anti allergy drug types
-mast cell stabilisers
-anti-histamines
-decongestants
what are the two types of inflammatory responses and give examples
-acute = cutes, bruises, sports injury
-chronic = RA, psoriasis, inflammatory bowel disease
what are the 4 signs of inflammation?
-redness
-heat
-swelling
-pain
what are the key stages of inflammatory cascades?
- Membrane phospholipids are released after injury and phospholipase enzyme hydrolyses these to arachidonic acid
- Cyclooxygenase enzyme then act on this acid to form prostanoids of which there are 3 types:
-prostacyclin
-prostaglandin e and f
-thromboxane - arachidonic acid also gets acted on by lipoxygenase enzyme to form leukotrienes
what inflammatory response does prostaglandin E cause?
-vasodilation = redness, warmness and blood vessel leakage with oedema
-sensitisation of tissues = irritation and pain
-fever
how do corticosteroids work?
inhibit the inflammatory response by inhibiting phospholipase A2 enzyme which means formation of arachidonic acid from membrane phospholipids is inhibited and so formation of prostaglandins AND leukotrienes are prevented
for corticosteroids,
give an example
where are they produced?
what is their roles
e.g. hydrocortisone
-produced in the adrenal cortex of the adrenal gland (outer part of adrenal gland)
-role is to maintain homeostasis by suppressing immune responses to allergy and inflammation
when would you use corticosteroids ocularly?
-substantial ocular inflammation, non infectious
-as a prophylactic measure to minimise the risk of inflammation in a susceptible eye e.g. in post op surgery
give examples of when you would use corticosteroids ocularly?
*Prevents further tissue damage (scarring/neovascularisation) resulting from long-term inflammation
*Blunt ocular trauma
*Anterior uveitis
*Episcleritis/scleritis
*Severe allergic conjunctivitis
give examples of ocular conditions where you’d use corticosteroids
-episcleritis (if its not going away on its own)
-Severe conjunctivitis in Stevens-Johnson Syndrome
-Neovascularisation in untreated Stevens-Johnson Syndrome
if a patient has a red eye and you are thinking of prescribing steroids, what do you need to do and why?
you need to rule out viral keratitis as you cannot prescribe corticosteroids to viral infections. This is because it would cause the host immune response to reduce which would cause the virus to proliferate even more.
why are corticosteroids not good for corneal infections?
as they already cause corneal thinning long term so it puts the patient at risk of corneal perforation
give some adverse reactions to short term use of corticosteroids
- Elevation of IOP (up to ~8 mmHg)
- Retard wound healing
- Immunosuppression
- Hide signs of infection
give some adverse reactions to long term use of corticosteroids
- Steroid-induced cataract
- Steroid-induced glaucoma
- Corneal thinning (risk of perforation)
give 5 steroidal drugs that can be used short term for local ocular inflammation
-betamethasone = drops every 1-2hrs
-dexamethasone = eye drops 4-6x daily (or hourly if severe)
-fluorometholone = 1hr for first 24-48hrs then 2-4x daily
-prednisolone = drops every 1-2hrs
-loteprednol = 1 or 2 drops 4x daily
how do NSAIDs work?
-inhibit cyclo-oxygenase enzyme (COX) which is necessary for synthesis of prostaglandins so that gets inhibited
(older NSAIDs like ibuprofen inhibit both cox1 and cox2 while newer nsaids offer selective inhibition of cox 2)
what are the 2 forms of COX enzyme and what’s the difference
-cox-1 = PG synthesis and normal homeostasis so in non inflamed tissue so better not to inhibit this
-cox-2 = involved in PG synthesis in inflammed tissue
give an example of an NSAID that only inhibits cox 2
celecoxib
what ocular indications would you use NSAIDs?
-post op cataract pxs to supress inflammation and prevent cystoid macular oedema
-argon laser trabeculoplasty (ART) as offers prophylactic prevention of inflammation
-seasonal allergic conjunctivitis
what are the contra-indications to NSAIDs?
*Avoid in patients on anticoagulant therapy
* Sensitivity to aspirin
* Gastro-intestinal problems
* Affects control of gastric secretions
* due to the inhibition of formation of
protective prostaglandins in the
gastrointestinal wall
* Increases acid secretion
* Gastric ulcer risk
why are nsaids not good at managing seasonal allergies?
-as they don’t inhibit leukotrienes
-Leukotrienes are produced by mast cells and can cause irritation like itching
name 3 topical ocular nsaids
-diclofenac 0.1%, good for post ops
-flurbiprofen 0.03%, good for frequent or recurrent episcleritis
-ketorolac 0.5%, good for post ops
what other therapeutic alternatives to steroids and nsaids are there to control inflammation?
-antimetabolites
-immune modulators
-biological blockers
who might you use antimetabolites for?
-sight threatening uveitis: bilateral, non infectious and failed to respond to steroid therapy
-patients that have intolerable side effects to systemic steroids
give 3 examples of antimetabolites
-Azathioprine (1mg/kg/day) – tablet
-Methotrexate (10-15mg/week in adults) – tablet ( Folic acid is co-administered to reduce bone marrow toxicity)
-Mycophenolate mofetil (1 g twice daily)
give 2 examples of immune modulators and what they’re for
-Ciclosporin (5mg/kg/day): Drug of choice for Behcet syndrome, intermediate uveitis, birdshot retinochoroidopathy, VKH syndrome, and idiopathic retinal vasculitis
-Tacrolimus (0.1-0.15mg/week in adults) tablet : An alternative to ciclosporin in intolerant or unresponsive patients
name 2 biological blockers
-IL-2 receptor antagonist
-Anti-tumour necrosis factor (TNF) alpha therapy
what happens in the allergic response cascase?
-allergen binds mast cells
-mast cells trigger degranulation causing mediators to be released of either histamine or cytokines in the acute and chronic response
-histamine = acute so triggers vasodilation which causes redness and oedema
-cytokines = chronic so causes mucosal infiltration of eosinophils, neutrophils, basophils and lymphocytes
for mast cells,
what are they?
where are they produced?
what do they contain?
how do they work?
-large cells similar to the basophil granulocyte class of leukocyte, found in connective tissue especially that near boundaries with the outside world
-produced in the bone marrow and leaves it in immature form and then matures when in connective tissue site
-contains granules rich in histamine and heparin
-Binding of allergen to two or more Immunoglobulin E molecules on mast
cells surface activates cell
what do mast cell stabilisers do?
prevent degranulation of mast cells so histamine and other inflammatory mediators do not get released however have no effect on histamine already released hence are most effective when administered before onset of an allergic response
name 3 mast cell stabilisers
-sodium cromoglicate = seasonal conjunctivitis
-lodoxamide = allergic conjunctivitis
what patients would you use anti allergy drugs on?
-seasonal allergic conjunctivitis in combo with antihistamine
-giant papillary conjunctivitis
what does histamine do?
- Dilation of blood vessels
- Contraction of smooth muscle
- Increased vascular permeability
what are the 3 histamine receptors and where are they found?
- H1
✓main receptor involved in the allergic response
✓Found in blood vessels walls and smooth muscle - H2
✓Found in stomach, heart, and blood vessels - H3
✓Found within CNS
what are the ocular responses to histamine?
-blood vessel dilation causing redness of conjunctiva
-incrrased blood vessel permeability causing oedema of conjunctiva and eyelids
-stimulation of sensory nerve endings causing itching
how do antihistamines work?
Usually specific for H1 class of histamine receptors
1. drug molecules compete with histamine to occupy histamine receptors - histamine receptor antagonists
2. prevent binding of histamine receptors
3. inflammatory response is inhibited
when may you use topical anti histamines ocularly?
-vernal conjucntivits due to the itching
what adverse ocular effects can be produced by topical antihistamines?
Stinging, lacrimation, irritation
name 6 topical ocular antihistamines
-antazoline - allergic conjunctivitis
-2nd gen anti histamines
-azelastine 0.05%
-ketitofen
-olopatadine: multidose w benzalkonium chloride
-epinastine: multidose w benzalkonium chloride
last three all for seasonal allergic conjunctivitis
what are the potential ocular side effects of antazoline?
- Transient stinging
- Upper lid retraction
- Pupil dilation
what are the symptoms of ocular manifestations of GCA?
-vision loss or disturbance
-diplopia due to the cranial nerve palsy
give 4 systemic complications of GCA
- Aortic aneurysm
- Aortic dissection
- Myocardial infarction (heart attack)
- stroke
give common symptoms of GCA
- Headaches
- Pain in shoulders
- Pain in the jaw when chewing
- Pain in the scalp e.g. when brushing the hair
- Fatigue, loss of appitite, loss of weight
- Feeling generally unwell
- Tenderness over the temporal arteries
what should you do about post catarcat op macula oedema?
Few days to a week post cataract surgery, most people will be found to have macular oedema and as long as it is not symptomatic or causing a large reduction in VA, then it should be self limiting and does not need treatment as it’s part of the normal inflammatory response
