deck 1 Flashcards
(84 cards)
1
Q
where are acute phase reactants made?
A
made in the liver, change production during acute inflammation
cyokines mediate acute phase response
(IL-1, IL6, TNF)
acute phase response in infection, trauma, burns, tissue infarction, advanced cancer, and immune mediated disease (subacute)
moderate changes after exercise/heatstroke
2
Q
What is the overall effect to eh acute phase response
A
goal is to protect host from damage - >however if it is too much, can harm patient (i.e. ARDS, macrophage activation syndrome, AIDS, amyloidosis, malignancy)
3
Q
Which acute phase reactant best reflects severe disease?
A
CRP - it recognizes pathogens and mediates action of complement and phagocytic cells, levels rise and fall quickly
4
Q
Which changes more slowly, eSR or CRP?
A
ESR changes more slowly, it is an indirect measure of acute phase reaction, changes more slowly than CRP, depends on fibrinogen and gammaglobulins
measures the height of the plasma layer after the RBCs settle in a tube of blood
5
Q
Which of the following decreases in an acute phase response?
a) complement
b) fibrinogen
c) transferrin
d) serum amyloid A
A
c) transferrin decreases, albumin and IGF-1 also decrease
markers that increase in acute phase response: CRP, ESR, complement, fibrinogen, coagulation proteins, ferritin, ceruloplasmin, haptoglobin, G-CSF, IL-1 receptor antagonist, serum amyloid A
6
Q
What is the type of anemia in chronic inflammatory disease?
A
nomocytic or microcytic anemia
7
Q
Type fo anemia in SLE?
A
autoimmune hemolytic anemia
8
Q
WBC count in SLE?
A
leukopenia with lymphopenia, neutropenia and/or thrombocytopenia in active SLE or medication related
9
Q
4 diseases with low complement levels
A
- SLE
- acute post infectious GN
- membrano-proliferative GN
- liver disease
**in general inflammation causes increased levels of complements
10
Q
2 types of ways that congenital complement deficiencies can present
A
- recurrent infections
2. unusual autoimmune disease
11
Q
Way to monitor disease activity in SLE?
A
measure C3 and C4->levels should FAL during a flare, become normal after treatment, if persistent low C3, think of lupus nephritis
12
Q
how many of the heathy population may have low titres of ANA?
A
up to 30% of normal healthy population may have low titres of ANA
non-rheum disease can also have ANA - infection, malignancy, meds
ANA are antinuclear antibodies - AKA antibodies against nuclear, nucleolar or perinuclear antigens
13
Q
A patient with JIA is ANA positive. What are 3 associated increased risks?
A
+ve ANA in JIA:
- higher risk of uveitis, asymmetric arthritis and early disease onset
14
Q
A patients being worked up for multiple diseases is negative for ANA. Is it likely they have SLE?
A
nope, negative ANA makes SLE unlikely
15
Q
A patient is ANA negative and has a clinical history consistent with JIA. Should you also ask for dsDNA to make the diagnosis?
A
nope, should only ask for dsDNA if ANA -ve and disease other than JIA is suspected
16
Q
Name 4 antibodies associated with SLE
A
- anti dsDNA
- anti Ro/SSA
- anti La /SSB
- anti Sm
- anti-RNP
17
Q
Name 3 diseases associated with anti Ro/La antibodies?
A
- SLE
- Neonatal Lupus erythematosus
- Sjogren
18
Q
3 diseases associated with anti-RNP?
A
- mixed connective tissue disease
- SLE
- systemic sclerosis
19
Q
2 diseases associated with anti-histone?
A
drug induced lupus
SLE
20
Q
anti-Scl70 associated with which which disease
A
diffuse systemic sclerosis
21
Q
anti-centromere antibodies, which disease?
A
CREST (aka limited systemic sclerosis)
22
Q
anti-Jo1 antibodies
A
polymyositis with interstitial lung disease, juvenile dermatomyositis (JDM)
23
Q
Which antibody in juvenile dermatomyositis suggests profound cardiac disease?
A
anti-SRP antibodies
meanwhile anti-Mi2 is good prognosis
24
Q
What is the PTT in antiphospholid syndrome?
A
prolonged PTT despite having increased risk of thrombosis
antiphospholipid antibodies - heterogeneous group of antibodies directed against cell
25
What are 3 secondary causes of antiphospholipid antibodies
1. Connective tissue disease
2. infection
3. drugs
**include lupus anticoagulant, anticardiopin, anti glycoprotein I
associated with increased risk of thrombosis (but prolongs PTT paradoxically)
26
True or false - most children with JIA are RF positive ?
false - only 5-10% of kids with JIA have it, (vs 85% of adults)
helps with classification and prognosis of JIA, do NOT use as a screening test (arthritis is a clinical diagnosis)
RF +ve suggsests more aggressive joint disease/disability
RF is an IgM autoantibody, reacts to Fc portion of IgG antibodies
27
Infectious diseases that can be positive for RF?
infection :
- subacute bacterial endocarditis, hep B/C, TB
may also be detected in chronic immune-complex mediated diseases, such as SLE, systemic sclerosis, Sjogren, cryoglobulinemia, chronic infection
28
What test has a high sensivitiy and specificity for primary small vessel systemic vasculitides
ANCA - aka antineutrophil cytoplasmic antibodies (ANCA)
| target antigens in cytoplasm of neutrophils, may be pathogenic by activating neutrophils (leads to chronic inflammation)
29
Which ANCA (pANCA or C ANCA) is associated with Wegener granulomatosis?
c-ANCA
| cANCA - cytoplasmic, proteinase -3 associated
30
Name 5 disease associated with pANCA?
1. microscopic polyangiitis
2. Churg-Strauss syndrome
3. UC
4. primary sclerosing cholangitis
5. SLE
pANCA is perinuclear - specific for myeloperoxidase (MPO)
31
Name 5 conditions that are associated with HLAB27
1. ankylosing spondylitis (in 90-95% of caucasian patients with this disease)
2. JIA - especially enthesitis related arthritis, psoriatic arthritis
3. IBD
4. acute anterior uveiits
5. reactive arthritis
HLAB27 may play a role in the pathogenesis of inflammatory disease; only 7-10% of general population has it, bit more in first nations
32
3 causes of dactilytis
1. JIA - especially enthesitis related arthritis and psoriatic
2. sickle cell
3. trauma
33
Raynaud phenominon -
1. connective tissue disease
| 2. vascular obstruction
34
2 diagnosis associated with night pain
1. malignancy
| 2. osteroid osteroma
35
What are the 7 subtypes of JIA?
1. oligoarthritis
2. polyarthritis (RF negative)
3. polyarthritis (RF positive)
4. systemic arthritis
5. enthesitis related arthritis
6. psoriatic arthritis
7. undifferentiated arthritis
JIA - arthritis of unknown aetiology before the 16th birthday, persists at least 6 weeks, other conditions are excluded ; classification is based on their symptoms in the first 6 months
36
most common subtype of JIA
oligoarthritis
typical patient - is young girl, positive NA< small number of swollen joints, most common knees, ankles, wrists or elbows
37
true or false - hip involvement is common in early oligoarthritis JIA
false - hip involvement is uncommon in oligoarticular JIA, especially early in disease
38
which joints are most commonly involved in JIA oligoarthritis
knees, ankles, wrists or elbows
definition 1-4 joints during first 6 months of disease
two categories:
persisten (never affects >4 joints); extended: affects more than 4 joints after first 6 months of disease
39
Which are the exclusions to a diagnosis of JIA oligoarthritis (despite arthritis of 1-4 joints lasting > 6 weeks)
psoriasis or a history of psoriasis in patient or first degree relative
arthritis in HLAB27 positive male after 6th birthday
(ank spond, ehthesitis related arthritis, sacroillitis with IBD or acute anterior uveitis or history of one of these disorders in 1st degree relative)
IgM RF on at least 2 occasions at least 3 months apart
presence of systemic JIA
40
How many patients with oligoarticular JIA have positive ANA
60-80%
| associated with increased risk of asymptomatic uveitis
41
How many joints are affected by polyarthritis JIA?
```
>5 joints
2 types - RF positive and RF negative
(RF negative is better prognosis)
exceptions are the same as for oligoarthritis
large and small joints are affected
RF negative (25% are ANA positive)
```
42
A teenage girl presents with symmetric arthritis involving 6 joints, including the PIP joints and MCP joints. They are RF positive and ANA positive. What type of JIA is most likely?
RF positive polyarthritis
essentially adult-type RA presenting in child or adolescent
symmetrical polyarthritis
ANA positive in 75%
may develop rheumatoid nodules, joint erosions, Felty syndrome
43
What is Felty syndrome?
A complication of RF positive polyarticular JIA, includes neutropenia and splenomegaly
44
What are the features of systemic JIA?
1. evanescent (non fixed erythematous rash)
2. generalized LN enlargement
3. HSM
4. serositis
accompanied by arthritis of 1 or more joints (may develop later) usually oligoarticular
once or twice daily fever spikes, return to baseline
Ddx includes Kawasaki, periodic fever, malignancy (leukaemia and lymphoma)
45
Which complication can occur with systemic JIA?
macrophage activation syndrome in 7% of patients
46
What is the definition of enthesitis related arthritis?
arthritis and enthesitis
OR
arthritis or enthesitis with at least 2 of the following:
1. presence or histyr of sacroiliac joint tenderness and/or inflammatory back pain, presence of HLAB27 antigen, onset of arthritis in a male over 6 years of age, acute (symptomatic) anterior uveitis, history of ankylosing spondylitis, enthesitis related arthritis, sacroillitis with IBD, or acute anterior uveitis in a first degree relateve (exception is psoriasis, RF positive, systemic JIA)
47
A 7 year old boy presents with achilles tendinitis and dactylics. What diagnosis should you consider?
enthesitis related arthritis
usually occurs in boys >6 years old, with family history, hallmark is enthesitis, most common sites are insertion of achilles tendon, plantar fascia, patellar tendon, and quad tendon
most commonly affects lower extremities, including hips, axial invoelemtn is later
other manifestation: - tarsi tis, dactilytis,
CAN get anterior uveitis (eye pain and redness)
48
Criteria for psoriatic arthritis?
1. arthritis and psoriasis
2. arthritis and least 2 of the following:
- dactylitis
- nail pitting or onychollysis
- psoriasis in a first degree relative
(often can get psoriasis after the arthritis)
arthritis is large and small joints
49
4 goals of therapy for JIA
```
1. eliminate inflammation
2 prevent joint damage
3. promote normal growth and development as well as normal function
4. minimize medication toxicity
multi D approach important
```
50
Which speciality (other than rheumatology0 should you refer patients with JIA to?
opthalmology - need an eye exam
51
Which type of arthritis has a increased risk of asymptomatic uveitis?
oligoarthritis with positive ANA
52
2 1st line treatment for oligoarticular arthritis
NSAIDS
| intra-articular steroid injection
53
If NSAID and steroid injection fails to cure the oligoarticular arthritis , what to do next?
consider intermittent IAC (for persistent oligoarticular arthritis) or methotrexate/other second line agent
if evolves into polyarticulr arthritis, then follow the algorithm for that
54
1st line treatment for polyarticular arthritis?
NSAIDS
| intra-articular steroid injfections
55
2nd line for polyarticular arthritis
nethrotrexate, leflunomide (pyrimidine synthesis inhibitor), sulfasalazine
56
3rd line treatment for polyarticular arthritis
1. biologic anti TNF therapy
57
Treatment for systemic arthritis
NSAID
severe disease - biology (IL-1 or antiIL6) or steroids - can add the biologics early with the new recommendations for JIA
58
How much of lupus is diagnosed before 16 year old?
15-20% of children diagnosed before age 16
59
How many criteria do you need for diagnosis of SLE?
4/11 criteria
60
What are the 11 criteria for SLE?
1. malar rash
2. discoid rash (rare in chilren)
3. photosensitivity
4. oral or nasal mucocutaneous ulcerations
5. non-erosive arthritis
6. nephritis - proteinuria or cellular casts
7. encephalopathy - seizures and/or psychosis
8. pleurites or pericarditis
9. cytopenia
10. positive ANA
11. positive immune serology anti DsDNA, anti Sm, anti-phospholipid antibodies
61
What are the possible cytopenias in SLE?
autoimmune hemolytic anemia (Coombs posiive)
thrombocytopenia
leukopenia/lymphopenia
62
How sensitive and specific are the 11 criteria for lupus?
>95% sensitive and specific (initially was designed for research studies, but beucase they worked for diagnosis, kept being used)
63
What are some associated features of lupus that are not part of the 11 criteria mentioned above?
```
constitutional symptoms
other rashes
polyarthralgia (**note this isn't a criteria)
Raynaud phenomenon
lymphadenopathy
hepatomegaly, splenomegaly
hypertension
```
64
Lab features of SLE
1. elevated ESR, NORMAL CRP
2. low complement levels
3. elevated IgG levels
4. other autoantibodies - anti-Ro, anti-La, anti RNP, RF
65
3 things that are more likely with paediatric presentation of SLE vs adult?
1. more likely to have active disease at presentation and over time
2. more likely to have active renal disease
3. more intensive drug therapy, more damage
can be different presentation in teens - consider in teenage females with polyarthritis, fever, rash and constitutional symptoms, ITP with positive ANA, unusual arterial or venous thrombosis, chorea
66
Treatment of SLE
based on organ involvement
1. hydroxychloroquine - standard therapy, decreases flares (# and severity), improves serum lipid
2. steroids - often initial therapy - sometimes do pulse therapy for severe lupus nephritis, hematologic crisis or CNS disease
3. azathioprine (used for heme and renal manifestations)
4. cellcept - use for hematologic, renal and CNS manifestations
5. cyclophophosphamide - severe renal and CNS manifestations
6. rituximab - for resistant thrombocytopenia
67
What is the 10 year survival for SLE?
relapse and remitting, 10 year survival>90%
cause of death: INFECTION, renal, CNS, cardiac and pulmonary disease
additional morbidity from disease/treatment includes:
- early onset CAD, bone disease ->osteopenia, AVN, malignancy
68
True or false - most mothers of babies with neonatal lupus erythromatosus have clinical lupus
```
not necessarily, they can have
1. SLE
2. Sjogren syndrome
other autoimmune diseases
mother may also be heathy with no known autoimmune disease
```
69
What causes neonatal lupus erythematosus
passage of maternal autoantibodies via the placenta
anti-Ro and anti-La antibodies
need the autoantibodies but not sufficient to cause NLE on their own - (some mom's with autoantibodies have healthy babies _ 1-2% of mother with anti-Ro/La have NLE
70
A baby is born with congenital heart block, the mother wants to know how likely that her next baby will be affected by the condition?
16% - higher risk for subsequent children once once child has been affected (16% for subsequent siblings of child with congenital heart block)
71
Clinical manifestations of neonatal lupus? - systems affected
1. cardiac - complete congenital heart block, can lead to CHF, fetal hydrous, intrauterine death; can also get less severe conduction abnormalities, carditis
2. skin - rash (face and scalp, not malar)
3. hematologic
4. hepatic
5. neurological
72
Cardiac manifestations of neonatal lupus?
complete congenital heart block->BAD
CHF, fetal hydrops, intrauterine death
can get less severe conduction abnormalities, carditis also
73
A 2 week old baby presents with a discoid facial rash and the mom has a history of lupus. What can you tell the mom about the course of the rash
classic NLE rash: annular, erythematous, papulosquamous rash, with find scale and central clearing
predisposed for face and scalp (not malar distribution), typically photosensitive, dermatitis may present at birth, more commonly within the first few weeks of life
new lesions for severe months, rarely after 6 months, typically health without scarring
telangiectasias 6-12 months of age, may not be in areas affected by previous rash
Treatment: if classic doesn't need treatment should resolve, steroids may help with healing but increase risk of telengiectasias
74
most common cell line affected in neonatal lupus?
thrombocytopenia most common
neutropenia and anemia less common
usually resolve without sequelae, rarely needs treatment
75
What are the hepatic manifestations of neonatal lupus?
cholestatic hepatitis with mild-moderately elevated liver enzymes
hepatomegaly
usually resolve by 6 months
76
neurological manifestations of neonatal lupus?
unclear clinical significance,
include macrocephaly, hydrocephalus, spastic paraparesis, asymptomatic neuroimaging abnormalities, vasculopathy, clinical significance still unclear
77
pregnant mom with lupus, baby has bradycardia. What management?
1. fetal echo to look for heart block
2. may treat with dexamethasone/sympathomimetics
if complete heart block, may need pacemaker
need to monitor future pregnancies - especially for heart rate
78
What are some secondary causes of antiphospholipis syndrome?
1. SLE
2. other autoimmune diseases
3. drugs/viral infections (i.e. HIV)
can have primary APS without underlying disease
79
more likely to have venous or arterial thrombosis in APS?
more likely to have venous thrombosis (60%)
arterial (30%), small vessel thrombosis (5%)
mixed thrombosis (2%)
80
manifestations of antiphospholipd syndrome
thrombotic manifestations
- include vascular thrombosis, pregnancy morbidity≥ 3 consecutive unexplained spontaneous abortions before 10 wks gestation, or
≥ 1 unexplained fetal loss beyond 10 wks gestation, or
≥ 1 premature birth before 34 wks gestation due to severe pre-eclampsia, eclampsia, or placental insufficiency
hematologic
skin
nonthrombotic neurological
81
What are the lab criteria for APS syndrome?
1. medium to high anticardiolipin (IgG or IgM)on>/=2 occasions at least 6 weeks apart
2. moderate ->high titres antibodies to beta2glycoprotein - 2 occasions 6 weeks apart
3. lupus anticoagulant >2 times 6 weeks apart
definite APS - one clinical plus 1 lab criteria
82
Other clinical features of APS?
```
livedo reticularis
cardiac valve disease - Libman-Sachs endocarditis
chorea
seizures
transient cerebral ischemia
transverse myelopathy
```
83
A woman has a history of 3 recurrent abortions and positive VDRL. What condition should you think of?
antiphospholipid syndrome
| can cause false positive VDRL
84
Other
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