key points AI diseases Flashcards
SS primary
no CT disease
SS triad
exocrinopathy - dryness mouth and eyes
fatigue
joint pain
SS epidemiology
usually 40-60yrs
F
SS aetiology
infections
biological factors
chemical
genetic - HLA association
SS proposed immunopathogenic mechanisms
microbial trigger destroys SG epithelium autoantigens differentiation of B cells into plasma cells auto-ABs form complex with auto Ags captured by DCs - T1 interferon activation of cytotoxic CD8
innate and adaptive
oral S+S SS
salivary hypofct caries fungal infections oral trauma lip dryness orofacial pain dysphagia dysgeusia swollen SGs GORD oral lesions of AI aetiology
SS systemic manifestations
30-40% constitutional LNs renal - interstitial nephritis articular - arthralgias cutaneous peripheral neuropathy muscular - myositis pulmonary glandular CNS
SS ESSDAI
clinical index to measure disease activity in pts w primary SS
each has a weighting - give score depending on severity
SS salivary hypofct/dysfct
diminished secretions on palpation
thicker/opaque/viscous secretions
recurrent SG infection
enlarged SGs in 30% (parotid)
SS caries
hyposalivation - reduced IgA secretion
- AB responsible for oral mucosal immunity that prevents caries
saliva in pSS not effective buffer
cervical and other atypical sites e.g. lingual surface, incisal edge and cusps
what fungal infection is prevalent in SS?
candidiasis
SS AI/immunomediated lesions
oral LP/lichenoid lesions
RAS
MMP
PV
secondary SS
when pt already has another AI disease then presents with extreme dryness of the eyes and mouth CT disease (SLE, RA, systemic sclerosis)
SS eye
dry eye extraglandular ocular complications - corneal inflammation - conjunctival inflammation - uveitis - scleritis/episcleritis - optic neuritis - retinal vasculitis
SS autoABs
anti-SSA ABs - antiRo
anti-SSB ABs - antiLa
present in 2/3 pts
SWSF >0.7ml/min
normal/mild dysfct
non-pharmacological stimulation
(saliva subs/pharmacological stimulation)
SWSF 0.1-0.7ml/min
mod dysfct
non-pharmacological/pharmacological stimulation
(saliva substitutes)
SWSF <0.1ml/min
severe dysfct
saliva substitutes
SS classification criteria - American College of Rheumatology/European League against Rheumatism
inclusion criteria
≥1
daily, persistent, troublesome dry eyes >3m?
recurrent sensation sand/gravel in eyes?
use tear substitutes ≥3 times daily?
daily feeling of dry mouth for >3m?
freq drink liquids to aid swallowing dry food?
or when suspicion of SS from EULAR SS DAI (≥1 positive)
SS classification criteria - American College of Rheumatology/European League against Rheumatism exclusion criteria
history of H+N radio active Hep C AIDS sarcoidosis amyloidosis GvHD IgG4-related disease
SS classification criteria - American College of Rheumatology/European League against Rheumatism - what do you need to score?
meet inclusion criteria
no exclusion criteria
score ≥4
SS classification criteria - American College of Rheumatology/European League against Rheumatism - scoring
biopsy - 3 antiSSA/Ro + - 3 ocular staining score ≥5 - 1 schirmer's test ≤5mm/min - 1 UWSF ≤0.1ml/min - 1
biopsy requirements SS
labial SG with focal lymphatic sialadenitis and focus score of ≥1 foci/4mm2
- ≥1 dense aggregates of ≥50 lymphocytes usually located in perivascular or periductal locations
biopsy technique SS
≥5 minor glands, L lip in paramedian region, incision parallel to labial frenum, identify minor gland, lift, remove, suture
SS non-pharmacological stimulation
gustatory stimulants: SF acidic candies, lozenges
mechanical stimulants: SF chewing gum
SS caries prevention
freq recall 4-6m OH F non-F remineralising agents salivary stimulation AM agents e.g. CHX
why is pilocarpine not always possible?
salivary residual secretory capacity needed - still need fct parenchyma
pilocarpine dose
5mg lozenges
3-6 daily
pilocarpine contraindications
uncontrolled asthma/COPD uncontrolled cardiorenal disease narrow-angle closure glaucoma gall bladder stones acute iritis
main primary sites of lymphoma in primary SS
SALIVARY GLANDS (parotid) lungs, gastric, ocular, oral/ENT, spleen
lymphoma risk in SS
risk of haematological malignancy most B-cell origin 3 subtypes - MALT lymphoma - DLBCL - MZL small number get non-B-cell haematological cancers - myeloid leukaemia, Hodgkin disease or T/NK cell lymphoma
test regularly (1-2yrs, high risk 6m)
SS risk factors for lymphoma
recurrent swelling of parotid glands splenomegaly/lymphadenopathy purpura > on ESSDAI RF cryoglobulinaemia low C4 level CD4 T-cell lymphocytopenia presence of ectopic germinal centres focus score of >3 germinal mutations in TNF AIP3
SS tx
inhibit proinflammatory cytokines - infliximab
interfere w T1 interferon production - hydroxychloroquine
immunobiologics - rituximab, infliximab
sicca syndrome
partial SS findings
American European Consensus Group Revised International Criteria SS
1 - dry eyes subjective 2 - dry eyes objective 3 - dry mouth subjective 4 - dry mouth objective 5 - autoAB findings 6 - histopathology
≥4 positive criteria (must inc 5 and/or 6)
T1 hypersensitivity
IgE - anaphylaxis
T2 hypersensitivity
IgG/M - cytotoxic - AgAB
T3 hypersensitivity
IgG/M - immune complex deposition (Ag-Ab)
T4 hypersensitivity
T cell mediated (delayed type)
what type of blister is pemphigus?
intraepithelial
what hypersensitivity reaction is pemphigus?
T2 - cytotoxic
Ag-Ab reaction - destruction of desmoglein
damage to LP
IgG Abs form
pemphigus HP
take perilesional biopsy of area not ulcerated/blistered - as won’t have epithelium in ulcer
acantholysis
suprabasal split
tzank cells
basal cells still fully attached by hemidesmosomes
acantholysis
spaces between spinous cells
tzank cells
in pemphigus
epithelial cells fall off into blister/bullae
DIF
tissue biopsy
usually for diagnosis
AB and fluorophore
IIF
serum
usually to measure ABs but can be used for diagnosis
can monitor progress and response to therapies
unlabelled Ab (primary) and supporting Ab with fluorophore (secondary)
positive DIF pemphigus
basket weave pattern
reflect where you get Ag-Ab reaction
grey areas - intraepithelial split/cleft
desmosomes
positive DIF pemphigoid
linear pattern
in hemidesmosomes - basal cell layer
what type of blister is pemphigoid?
subepithelial
what type of hypersensitivity reaction is pemphigoid?
T2
pemphigoid HP
sub basal split
no acantholysis or tzank cells
LP shows inflammation - inflammatory cells
eosinophils characteristic of bullous pemphigoid not so obvious in MMP
why do many diseases affect both skin and oral/genital mucosa?
they share many common antigens and epitopes
antigens - provoke immune response but epitope binds
epitopes - part of Ag that binds to Ab
general pathogenesis of AMBDs
auto-AB attack on skin components causing loss of cell-cell adhesion - desmosomes - hemidesmosomes (basal cell layer) split/cleft forms in skin - fills with inflammatory exudate - vesicle (<5mm)/bulla (>5mm)
SS histology minor gland
focal lymphocytic sialadenitis acinar loss fibrosis focal collections of lymphocytes (50+) - ≥1 collection per 4mm2
SS histology major gland
lymphocytic infiltrate, extends to whole lobules
epithelial hyperplasia of duct (myoepithelial islands) eventually occludes
atrophy of acini
pemphigus pathogenesis
autoABs against desmoglein intraepithelial blister acantholysis autoABs deposited in epithelium anti-Dsg3 IgF complement activated and plasmin
pemphigus classification
vulgaris foliaceous drug-induced paraneoplastic IgA
age pemphigus
40-60s
pemphigus foliaceous
superficial form - skin
lacks mucosal involvement
anti-Dsg1
oral lesions rare
pemphigus prognosis
untxed often fatal - metabolic consequences, dehydration/infection
mucosal lesions may persist after skin controlled
- topical CS/tacrolimus
now often complications of tx major cause of death - CS, MAbs