Autoinflamm / AOSD Flashcards
** AOSD manifestations **
(Double)/Quotidian fevers (>39 daily but returns to normal)
-Arthralgia/arthritis/myalgia
-Transient rash
-Prodromal sore throat (perichondritis of cricothyroid cartilage)
-LN, Weight loss, HSM
-Pleuritis/pericarditis
-Pneumonitis
-Abdo pain
Double quotidian fever ddx
-AOSD
-Kawasaki
-Kala-azar
-Mixed Malaria
-TB (miliary)
-Gonococcal endocarditis
AOSD Rash description
Evanescent (elicited w/ heat eg fever, shower)
-Salmon colored,
-Macular/maculopapular,
-Nonpruritic
-Koebner phenomenon
-Can be atypical w/ urticaria
AOSD rash biopsy
Dermal edema
-Perivascular mononuclear cell infiltrate
AOSD lab features
-Ferritin>1000ng/mL
-Soluble IL-2 R
-Increased liver enzymes
-Hypoalbuminemia, Anemia
-Increased ESR/CRP, WBC (neut), Plt
High ferritin DDX
-AOSD, MAS
-SLE, CAPS
-Infection (HIV, TB, CMV), Septic shock
-Cancer (Breast, lung, liver, colon, prostate, melanoma, lymphoma, liver mets)
Pathophys high ferritin in AOSD
IL6, IL18, TNF induce heme degrading enzyme (heme oxygenase) on macrophages and endothelial cells →
- Iron release from heme →
- Ferritin synthesis
AOSD pathophys
PAMP/DAMP binds TLR on macrophage/ neutrophil → inflammasome activation → caspase activation and overproduction of IL1B
-IL1B further activates macrophages/ neutrophils → more proinflamm cytokines (IL6,8,17,18, TNF)
-Regulatory antinflamm mech (reg T cells or IL10) may be defective
** Yamaguchi criteria including exclusions**
5+ (including at least 2 major):
-Major:
-Quotidian Fever 39 >1wk
-Arthralgia/arthritis >2 wks
-Salmon evanescent rash
-Leukocytosis >10k w/ >80% neuts
-Minor:
-Sore throat
-Lymphadenopathy
-Hepato or splenomegaly
-Abnormal liver enzymes
-NEGATIVE RF and ANA
-*Exclusion: SLE, infxn, Cancer, sweet’s, schnitzler, autoinflamm, D rxns
Unusual AOSD Derm manifestations
Alopecia
-Mucosal ulcers
-Subcut nodules
AOSD Unusual Cardiac Manifestations
Myopericarditis
Tamponade
Heart block
AOSD Unusual Pulm Manifestations
Pharyngitis
-ILD
-pHTN
AOSD Unusual GI Manifestations
Necrotizing lymphadenitis (Kikuchi) – >A abdo pain
-Acute liver failure
AOSD Unusual Heme Manifestations
-Hemolytic anemia
-TTP
-MAS, DIC
AOSD Unusual Neuro Manifestations
Aseptic meningitis
-Sensorineural hearing loss
-Periph neuropathy
-Amyotrophy
AOSD Unusual Ocular Manifestations
Orbital pseudotumor
-Uveitis
AOSD Unusual Renal Manifestations
Interstitial nephritis
-Amyloidosis
AOSD Tx
Mild (fever, arthralgia): Naproxen 500BID → pred 0.5/mg/kg/d if no fx s/p 2wks
-Mod (high fever, disabling arthritis, mild organ involvement): high dose pred 1mg/kg/d
– Add MTX if MSK and trouble tapering
-Severe (liver necrosis, tamponade, MAS, DIC): pulse steroids + early biologic
-Resistant (ongoing pred >20mg/d despite DMARD): Biologic
AOSD biologic options
AntiTNF (better for chronic articular w/ few systemic)
-IL1i (anakinra, canakinumab, rilonacept)
-IL6i (toci) better for systemic
Other options in AOSD if resistant to 1st line biologics
RItux,
-Abatacept,
-IVIG,
-Stem cell transplant
Poor prognostic signs for chronic AOSD
Polyarthritis
-Large joint involvement (shoulder/hip)
-Elevated ferritin at onset
Cause of death Stills
-Infxn
-Heme: DIC, TTP, MAS
-Status epilepticus
-ARDS
-Liver/heart failure
-Amyloid
** Diff between MAS and AOSD **
-Fever nonremitting
-Rapid cytopenias due to phagocytosis of hematopoeitc cells by macrophages in BM and reticulendothelial system
-Hemorrhagic manifestations: DIC, GIB,
-HyperTG
** MAS lab abnormalities **
Cytopenias
-High ferritin, TG, soluble IL2R (CD25)levels
-High liver enzymes,
-Consumptive coagulopathy (DIC w/ high PT),
-Low fibrinogen → LOW ESR,
MAS pathology
BM aspirate and biopsies of LN, liver, spleen show hemophagocytosis by macrophages
MAS Tx
High dose GC
-Cyclosporine
-Etoposide
-Biologics (IL1i, TNFi)
-DMARD (MTX, AZA, MMF)
-IVIG
MAS IX
PCR for active EBV or other viral (CMV, Parvo)
Characteristics of AutoInflamm
INNATE immune system (no autoantibodies)
-Antigen INDEPENDENT (no infxn or autoimmunity)
-Periodic fever
** Autoinflamm or periodic fever pathogenesis **
– Activates Inflamamsome and caspase 1 to cleave pro IL1b
– Excess IL1B production cause endothelial activation, hepatocyte and acute phase reactant production, and activation of NFkb activating IL1, 6, TNF
Autoinflamm manifestations
Continuous, irregular, or regular flares of fever, ESR/CRP/WBC, and sx involving joints, organs, skin, eyes
-Self resolving and asymptomatic w/ normal labs in btwn
** Recurrent fever DDX**
Cyclic neutropenia
-Hypothalamic dz
-Infection: hidden foci (eg aortoenteric), borrelia, malaria, whipple, recurrent reinfection (host defense defect, immunodeficiency)
-Noninfectious inflamm: behcet, sJIA/AOSD, sarcoid, IBD, Sweet, CRMO, Schnitzler
-Vascular - DVT/PE
-Ca: Leuk, lymphoma, solid tumor (pheo, neuroblastoma, colon, RCC), paraneoplastic
** Name five periodic fever syndromes. Name three presentations. Name two that present in childhood. Which part of the immune system is activated? What is the pathway?**
FMF
-TRAPS
-CHILDHOOD HIDS
-CAPS (FCAS, MWS, NOMID)
-PFAPA
-PAPA
-Blaiu
-DIRA