Autoinflammatory Syndromes Flashcards
Which syndrome is associated with erysipeloid erythema (an erythematous rash around the foot/ankle during flares)?
Familial Mediterannean Fever
What are key characteristics and treatment for Familial Mediterranean Fever?
- 1-3 days of fever with serositis, arthritis, or rash (erysipeloid erythema).
- peritonitis, amyloidosis
- Jewish, Armenian, Arab, Turkish, Italian are high risk
- recessive mutations in MEFV (encodes pyrin)
- Tx: colchicine, IL-1 inhibitors
What are key characteristics and treatment for TNF Receptor-Associated Periodic Syndrome (TRAPS)?
-fever for up to weeks (longest fever episodes of autoinflammatory syndromes), serositis, rash
-migratory rash and periorbital edema are characteristic
-DOMINANT mutations in TNFRSF1A
-renal amyloidosis
Tx: Colichicine usu NOT EFFECTIVE however corticosteroids, etanercept, and IL-1 blockade (anakinra, canakinumab) are effective in various settings
*adalimumab, infliximab cause FLARE of disease (monoclonal antibodies against TNF)
What are key characteristics and treatment for Hyper-IgD with periodic fever syndrome (HIDS)?
-always onset childhood w/ vaccinations; onset 1st year of life. Stress can trigger flares too.
-recessive mutations in MVK gene (mevalonate kinase), which is involved in cholesterol and steroid synthesis
-thought that a decrease in isoprenoids, such as geranyl pyrophosphate, leads to overproduction of IL-1beta
-painful cervical adenopathy, aphthous ulcers, abdominal pain, arthritis, rash
-amyloidosis is RARE
-Dutch, northern europeans
-Can have normal IgD. Serum IgD does not correlate with flares
Tx: IL-1 blockade (anakinra, canakinumab)
What are the 3 different CAPS diseases that are caused by mutations in CIAS1? (CIAS1 Associated Periodic Fever Syndromes).
FCAS - Familial Cold Autoinflammatory Syndrome
Muckle-Wells
NOMID/CINCA (neonatal onset multisystem inflammatory disease/chronic infantile neurological cutaneous and articular)
All 3 have fever + urticarial rash, mutations in NLRP3 aka CIAS1 (cryopyrin) –> excessive IL-1beta
What are key characteristics and treatment for FCAS - Familial Cold Autoinflammatory Syndrome?
-Dominant mutations in CIAS1 aka NLRP3 (cryopyrin)
-fever, urticarial rash: Flare with generalized exposure to cold–negative ice cube test but positive evaporative cooling test
-Rash 2hrs after exposure, last 12 hrs
-Not true urticaria: neutrophils, not mast cells
-Onset usu in first 6 mo of life, can be right after delivery (cold room)
-Amyloidosis is rare
Tx: IL-1 inhibition (Anakinra)
What are key characteristics and treatment for Muckle-Wells Syndrome?
-Dominant mutations in CIAS1 aka NLRP3 (cryopyrin)
-fever, urticarial rash
-arthritis
-sensorineural deafness
-amyloidosis
Tx: IL-1 inhibition
What are key characteristics and treatment for NOMID/CINCA (Neonatal Onset Multisystem Inflammatory Disease)
-Dominant mutations in CIAS1 aka NLRP3 (cryopyrin)
-fever, urticarial rash
-bony overgrowth
-CNS disease (papilledema, chronic meningitis, hearing loss)
Tx: IL-1 inhibition
What are key characteristics and treatment for DIRA (deficiency of IL-1 receptor antagonist)?
- neonatal onset
- systemic inflammation (elevation ESR, CRP, cytokine)
- multifocal osteomyelitis
- periosteitis
- skin pustulosis (discrete lesions to confluent lesions)
- RESPONSE TO ANAKINRA HUGE
What are key characteristics and treatment for PAPA syndrome?
- Pyogenic Arthritis
- Pyoderma gangrenosum
- Acne - cystic and scarring
- Dominant mutation in PSTPIP1 (interacts with pyrin to cause increased IL-1beta activation)
- Tx: steroids, TNF blockade, IL-1 blockade
What are key characteristics and treatment for DADA2 syndrome?
- AR mutation in CECR1 -> deficiency in ADA2
- intermittent fevers
- early onset lacunar strokes (recurrent) and other neurologic issues
- livedoid rash
- systemic vasculopathy (lots of TNF deposition in blood vessels), polyarteritis nodosa
- mild immunodeficiency (esp IgM)
- hematologic abnormalities
- TNF blockade may help prevent strokes
- anticoag and anti-platelet therapies should be AVOIDED
- BMT may be helpful in some
What are key characteristics and treatment for CANDLE (Chronic Atypical Neutrophilic Dermatosis with Lipodystrophy and Elevated temperatures) syndrome?
-excessive type 1 interferon production from mutation in proteasome subunit beta type 8
-nodular erythema
-panniculitis
-lipoatrophy, intra-abdominal fat deposition
-myositis
-Basal ganglion and soft tissue calcifications
Tx: JAK kinase inhibitors
What are key characteristics of SAVI (STING associated vasculopathy in infancy)?
- vasculitis
- gangrene
- lung fibrosis
What are key characteristics and treatment for PFAPA (Periodic Fevers with aphthous stomatitis, pharyngitis, and adenitis)?
- most common periodic fever syndrome in children
- no gene identified yet
- duration 3-6 days, every 3-8 weeks often with strict “clockwork” periodicity
- dramatic response to steroids, can give as a “test”
- tonsillectomy can cause temporary cessation
- cimetidine helpful in 30% of pts
- intermittent anakinra helpful in aborting episodes
- children tend to outgrow this
What are key characteristics and treatment for Behcet’s Disease?
-oral ulcerations, eye lesions, skin lesions, genital ulcerations
-Dx criteria: recurrent oral ulcers at least 3x/year, plus two of the following
-recurrent genital ulcers
-eye lesions (uveitis or retinal vasculitis)
-skin lesions (e. nodosum, papulopustular lesions or acneiform nodules)
-pathergy (exaggerated skin injury)
-Assoc with: GI disease (diarrhea, abd pain, ulcerations), neurologic disease, vascular disease, HLA-B51 prevalence, haploinsufficiency of A20 (HA20)
Tx: colchicine, prednisone, targeted organ manifestations
