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HDT 3.1 > Autoinflammatory disorders > Flashcards

Autoinflammatory disorders Flashcards

1
Q

what are autoinflammatory disorders?

A

A group of diseases that manifest as recurrent fevers and episodes of inflammation
* Presence of skin rashes and joint inflammation and No infection
* Absence of auto- antibodies that are typical of autoimmune diseases
* Typically high acute phase
responses and involvement of innate
immune system

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2
Q

what are some examples of auto inflammatory conditions?

A

IBD
behcet’s disease
gout
psoriasis

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3
Q

what characteristics for auto inflammatory disease compared to autoimmune diseases?

A

inflammatory:
- use of innate immunity
-prevalent in both sex

immune:
- t and b cell involvement
- female predominantly

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4
Q

what are hereditary fever syndromes?

A

disorders characterised by episodic fevers (irregular fevers)

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5
Q

what are some examples of hereditary fever syndrome?

A

Familial Mediterranean Fever(FMF)
HIDS (hyperimmunoglobulinemia D syndrome)
TNF receptor- associated periodic syndrome (TRAPS)

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6
Q

what is episodic fevers?

A

irregular fevers

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7
Q

how does hereditary fever syndrome occur?

A

mutations in genes that are linked to dysfunction in an innate immune system

> 180 mutations in MEFV gene = abnormal pyrin protein

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8
Q

how is hereditary fever syndrome detected?

A

blood increases acute phase response proteins
- elevated ESR/CRP/ serum amyloid A (SAA)

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9
Q

what are the symptoms of hereditary fever syndrome?

A

Episodic fever lasting 12 hours to 3 days
Severe abdominal pain
Joint swelling and inflammation
Skin rashes-often on feet and lower legs
FMF can also lead to amyloidosis (build up of amyloid in kidneys), which can result in kidney failure

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10
Q

what is pyrin?

A

pattern recognition receptor

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11
Q

how does familia mediterranean fever (FMF) occur?

A

> 180 mutations in MEFV gene = abnormal pyrin protein

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12
Q

what are the symptoms of hyperimmunoglobulinemia D syndrome (HIDS/MKD)?

A

Periodic fever, typically lasting 1 week
Rash
Severe abdominal pain
Joint pain and inflammation
Enlarged liver and spleen
Swollen lymph nodes
High levels of IgD in blood

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13
Q

who is mainly succeptible to hyperimmunoglobulinemia D syndrome (HIDS/MKD)?

A

europeans

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14
Q

who is mainly succeptible to familia mediterranean fever (FMF)?

A

eastern mediterranean

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15
Q

who is mainly succeptible to TRAPS?

A

Europeans

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16
Q

what are the symptoms of TRAPS?

A
  • More persistent fever, typically lasting 1-4 weeks
  • Severe abdominal pain
  • Joint and muscle pain
  • Swollen eyes and conjunctivitis
  • Painful migrating rash on upper body and/or arms and legs
  • TRAPS can also lead to amyloidosis
17
Q

explain how FMF induces a disease state

A

mutated pyrin = activates NAPL3 inflammasome = activate Caspase-1 = secrete IL-1B = increase neutrophils to body cavities = inflammation induction

18
Q

explain how TRAPS induces a disease state

A

TNFR mutation = TNF receptor inactive = less soluble TNF-a ligand signalling = impaired TNF binding

19
Q

what is the treatment for hereditary disease?

A

FIRST LINE
symptomatic treatments - NSAIDs, GC’s to reduce pain/inflammation
& colchicine as a preventative
SECOND LINE
colchicine resistant - anti-IL-1B (anakinra/canakinumab/rilonacept)

20
Q

what are the drug characteristics of colchicine? and side effects

A

1-2 mg/daily
life long treatment
reduces long term risk of amyloidosis and kidney failure

SIDE EFFETS:
Gastrointestinal side-effects (nausea,
vomiting and diarrhoea)

21
Q

what is the mode of action of colchicine?

A

Inhibits the NALP3 inflammasome
* Reduces caspase-1 activation
* Results in a reduction in IL-1β release

Also inhibits neutrophil migration

22
Q

what can you give as an alternative for colchicine resistant pts?

A

ANTI-IL1B TREATMENT:
Rilonacept (Arcalyst)
* Fusion protein with domains of IL-
1β receptors.
* Acts to trap IL-1β (IL-1TRAP)
Canakinumab
* Monoclonal Antibody that mops
up IL-1β
Anakinra
* Recombinant protein that acts as a IL-1 receptor antagonist

23
Q

what can you give as an alternative for colchicine resistant pts ?

A

Rilonacept (Arcalyst)
* Fusion protein with domains of IL-
1β receptors.
* Acts to trap IL-1β (IL-1TRAP)
Canakinumab
* Monoclonal Antibody that mops
up IL-1β
Anakinra
* Recombinant protein that acts as a IL-1 receptor antagonist

24
Q

what are anti-TNF treatments?

A

Etanercept
* Dimeric fusion protein composed of
2x human TNF receptors fused to
Fc portion of IgG1.
* Acts as a decoy receptor for TNF

Infliximab
* Chimeric monoclonal antibody
* Binds to TNF

25
Q

what are the symptoms of adult onset stills disease (AOSD)?

A
  • Intermittent fever lasting a week
  • Arthritis/arthralgia
  • Salmon-coloured rash
  • Sore throat
  • Enlarged liver/spleen
  • Muscle pain
  • Blood results
  • Indicates liver dysfunction
  • increase in liver enzymes and ferritin But negative for auto-antibodies
26
Q

what is the first and second line treatment for AOSD?

A

1st line : NSAIDS/GCs to reduce pain/inflammation

2nd line: disease modifying treatments
- MTX
- IL-1B targeting agents for systemic AOSD
Rilonacept or canakinumab
- Anti-TNF for articular AOSD

27
Q

what is gout? and how is it caused?

A

Gout is the deposition of MonoSodium Urate (MSU) crystals in the joints
* excess uric acid production
* inefficient processing by the kidneys

28
Q

what are the common sites for gout to occur?

A
  • Most common in big toe, but can affect multiple joints
  • Common in knee, ankle, instep, elbow
  • Less common in shoulder, wrist, finger
  • In early stage disease, usually only 1-2
    joints are involved.
29
Q

what are the risk factors of gout?

A
  • Male gender (3.6 to 1)
  • Age
  • Diet -obesity/Metabolic syndrome
  • Higher prevalence in developed countries
  • Hypertension
  • Chronic Kidney Disease
  • Osteoarthritis
  • Genetics
30
Q

what are the two classes of gout/ MSU crystal production?

A
  1. over-production (10%)
  2. under-excretion (90%)

or
1. acute attacks
2. chronic gout

31
Q

how does over-production MSU crystal production occur?

A
  1. increase in dietary purines
    - meat (beef/pork/lamb) / seafood / beer / drinks with fructose
  2. increase purine synthesis
    - malignancy
    - HGPRT deficiency
32
Q

how does under-excretion MSU crystal production occur?

A

-renal failure
-diuretics
-hydrochlorothiazide (HTZ)
-aspirin

33
Q

what are acute attacks of gout?

A

Sudden onset, common during the night
Acute inflammation
Complete resolution 5-10 days
Usually only 1 joint affected

34
Q

what is chronic gout?

A

Polyarticular
* more frequent and involve multiple joints (polyarticular)
* Tophus (deposits of sodium urate)
- Joints / External ear /Kidneys (Lead to kidney stones Nephropathy)

35
Q

how do you detect gout?

A
  • Ultrasound of the joint can detect presence of MSU
  • X-rays of joint can detect Tophi deposits, calcifications and erosions
  • Blood rests to examine elevated levels of acute phase response proteins (ESR, CRP) and elevated uricemia
  • Joint fluid analysis - fluid is aspirated and MSU crystals observed by microscopy
36
Q

how does gout induce inflammation?

A
  1. MSU crystals phagocytose by macrophages
    • activation of inflammasomes and release of IL-1B
  2. Binding to TLR2/TLR4 on macrophage
    activation of NFkB, leads to activation of inflammasome and IL-1b release
37
Q

what is the treatment for acute attacks of gout?

A

1st line:
NSAIDs
colchicine used if NSAIDs are contraindicated
oral/inj corticosteroids

2nd line: canakinumab if frequent acute attacks

38
Q

what is the treatment for chronic gout?

A

Frequent occurrence and presence of tophi requires therapeutic management of hyperuricemia

  • Xanthine oxidase inhibitors (Allopuriniol, Febuxostat)
  • Uricosuric agents (e.g probenecid)

But not started during an attack since they can precipitate

39
Q

name Xanthine oxidase inhibitors used for gout

A

Allopuriniol, Febuxostat

HDT 3.1 (13 decks)

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