Autoinflammatory syndrome

Question 1

Familial MEditerranean Fever

Answer 1

• <20 yo, medierranean
• Short Fever (2-3d), peritoneal, pleuritis, rash, elevated CRP, ESR
• Can result in amyloidosis and renal failure
• Cause: Mutation in MEFV gene
  
  • produces Pyrin
  • Pyrin normally controls inflammation and shuts it off when needed
  • mutations lead to increased inflammation
• Amyloid A is overproduced
• autosomal recessive
• treatment: Cholchicine

Question 2

Hyper IgD (HIDS)

Answer 2

• Very rare, Netherlands, France, 4d, arthritis, skin leasions, adenopathy, diarrhea, elevated CRP, ESR, extremely high IgD
• less serious with age
• Autosomal recessive
• Treatment of HIDs = statins
• mutation in melovate Kinase (right after HMG-coA) - leads to decrease in metab gerylgeranylpyrophosphate and an increase in IL-1

Question 3

TNF receptor associated periodic syndrome (TRAPS)

Answer 3

• Autosomal Dominant, Northern European, 3 yo
• Fever >7 days, arthritis, conjunctivitis, chest pain, intense myalgias, rash, attacks every 6 weeks
• Can lead to amyloidosis is 15% of cases
• mutation in TNF receptor, makes it not recycled and always turned on.
• treatment - etanercept

Question 4

Cyropyrin Associated periodic syndromes (CAPS)

Answer 4

• NE, birth/infancy, autosomal DOM
• Fever 1-3 days, arthritis, conjunctivitis , urticarial rash, headaches, meningitis, leukocytis APR,
• can be triggered by cold, damp, stress
• some can develope amyloidosis or sensorineural deafness
• Mutation in the NLRP3 of the inflammasome, leads to increased IL-1 production
• Treat - IL-1 agonist (anakinra)

Question 5

Inflammasome

Answer 5

• NLRP1/3, ASC, CARD - caspase activation and recruitment domain
• Caspase-1 cleaves Pro-IL-1 to IL-1

Question 6

IL-1 proinflammatory functions

Answer 6

• induces COX and PGE2
• activates Hs proteins
• Stimulates other inflam cytokines - like TNF
• Acute phase reactants - CRP, serum amyloid A
• attracts neutrophils
• Fever

Question 7

Serum Amyloid A

Answer 7

• acute phase reactant protein from liver
• induced by IL-1 and IL-6
• stimulates IL-1 proudction
• activates inflammsome
• contributes to the formation of amyloids