Autoinflammatory Diseases
Rheumatology · Other Rheumatologic Diseases 🎯 Practice these cards
Autoinflammatory diseases are characterized by ____ and/or ____ inflammation and involve inherited or spontaneous mutation of genes that encode for ____.
Autoinflammatory diseases are characterized by episodic and/or persistent inflammation and involve inherited or spontaneous mutation of genes that encode for inflammatory responses. They are disorders of innate immunity (not antigen-specific autoimmunity); the classic forms are inflammasome/IL-1β driven.
FMF is the ____ autoinflammatory disease; it is caused by mutations of ____ (protein ____) with ____ inheritance.
Familial Mediterranean fever (the most common autoinflammatory disease) is caused by autosomal recessive mutations in MEFV encoding pyrin, leading to inflammasome activation: fever, arthritis, erysipeloid rash, and sterile peritonitis in 12–72 h attacks; renal AA amyloidosis may ensue.
The initial treatment of choice for FMF is daily oral ____, which prevents the development of ____; for colchicine-resistant FMF the highest-level evidence is for ____ inhibitors.
Daily oral colchicine (usual adult dose 1.2–1.8 mg/d; 2024 EULAR/PReS maxima 2 mg/d children, 3 mg/d adults) decreases attack frequency/intensity and PREVENTS AA amyloidosis in compliant patients; intermittent dosing is inferior. Colchicine-resistant FMF → IL-1 inhibitors (canakinumab FDA-approved).
TRAPS attacks characteristically last ____ (vs 12–72 h in FMF); two clinical clues are ____ with overlying erythema and ____ edema; the biologic class to AVOID is ____.
TRAPS: autosomal dominant TNFRSF1A (TNF receptor type 1) mutations; attacks last days to weeks (longest of the periodic fevers) with fever, serositis, migratory myalgia with overlying erythema, conjunctivitis/periorbital edema; ~15% develop amyloidosis. Treat with glucocorticoids, etanercept, or canakinumab (FDA-approved); AVOID monoclonal anti-TNF antibodies (may exacerbate attacks).
The three CAPS phenotypes, from mildest to most severe, are ____, ____, and ____; all are caused by mutations in ____.
Cryopyrin-associated periodic syndromes (all NLRP3/cryopyrin, autosomal dominant): FCAS (cold-triggered urticaria-like rash, 12–24 h attacks, onset <1 y) → Muckle-Wells (urticaria + progressive sensorineural deafness, amyloidosis risk) → NOMID/CINCA (continuous neonatal disease, chronic aseptic meningitis, deforming arthropathy). All respond dramatically to IL-1 blockade.
For FCAS/MWS the FDA-approved IL-1 agents are ____ and ____; for NOMID it is daily ____.
FDA-approved IL-1 regimens for CAPS: bimonthly canakinumab (anti-IL-1β mAb) and weekly rilonacept (IL-1 receptor fusion protein) for FCAS and MWS; daily anakinra (IL-1 receptor antagonist) for NOMID. ~1/3 of NOMID patients are somatic mosaics with negative germline testing — they respond just as well.
HIDS is now often called ____ deficiency; the two clinically distinctive features are painful ____ and ____ ulcers; serum ____ levels do not correlate with disease activity.
HIDS/MKD: autosomal recessive MVK mutations (northern European/Dutch); infancy-onset attacks lasting 3–5 days with painful cervical adenopathy, maculopapular rash (±palms/soles), aphthous ulcers; mechanism = RhoA mislocalization → pyrin inflammasome activation. Serum IgD does NOT track disease activity (urinary mevalonate always elevated during attacks). Canakinumab is FDA-approved.
Untreated, approximately ____% of TRAPS patients develop amyloidosis; in FMF the preventive drug is ____; the biochemical treatment target in AA amyloidosis is complete suppression of ____ (or CRP).
AA amyloidosis risk: FMF = high (colchicine prevents it); TRAPS ≈ 15% untreated; MWS and FCAS also carry risk (MWS > FCAS); NOMID includes amyloidosis among its complications. Monitoring goal in established amyloidosis: complete, sustained suppression of SAA/CRP.
Schnitzler syndrome is ____ (inherited/acquired); its hallmark gammopathy is monoclonal ____; treatment of choice is ____ inhibition.
Schnitzler syndrome: ACQUIRED autoinflammatory disease of middle age (51 ± 10 y) — daily fevers, urticarial rash, bone pain/arthritis, leukocytosis, lymphadenopathy, hepatosplenomegaly, and a hallmark monoclonal IgM-κ gammopathy (MGUS) that may evolve to Waldenström macroglobulinemia. Treatment of choice: IL-1 inhibition (anakinra or canakinumab).
VEXAS is caused by somatic mutations in ____ on the ____ chromosome; it predominantly affects ____ over age 50 and can mimic ____ (a cartilage disease) or MDS.
VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic): acquired autoinflammatory disease from myeloid-restricted somatic UBA1 mutations, mainly men >50 (~1 in 4,269 men over 50 carry associated variants). Presents as relapsing polychondritis, Sweet syndrome, vasculitis, or MDS with fevers and macrocytic anemia; marrow vacuoles in myeloid precursors. Described in 2020.
DADA2 is caused by recessive loss-of-function mutations in ____; its feared neurologic complication is early-onset ____; the drug class that prevents strokes is ____.
Deficiency of adenosine deaminase 2 (DADA2): recessive ADA2 loss-of-function → vasculopathy with livedoid rash, early-onset lacunar strokes, and/or polyarteritis nodosa, plus possible immunodeficiency or bone marrow failure. Diagnose with ADA2 enzyme activity + ADA2 sequencing. TNF inhibitors are highly effective at preventing strokes; HSCT for severe hematologic phenotypes (2023 international consensus).
The most common periodic fever syndrome in children is ____; its episodes tend to resolve by ____; one surgical option is ____.
PFAPA (periodic fever with aphthous stomatitis, pharyngitis, and cervical adenitis) is the most common periodic fever syndrome in children — clock-like regular episodes that tend to resolve by early adulthood; familial but non-Mendelian (IL12A/IL10/STAT4/CCR1-CCR3 susceptibility variants shared with Behçet spectrum). Options: intermittent glucocorticoids, colchicine, cimetidine, apremilast, or tonsillectomy/adenoidectomy.
Tap a card to flip it.