| What are auto-inflammatory syndromes? | Mutations in genes of inflammatory response, rare disorders, early onset few hour to decades of life, delayed dx, recurrent flares (systemic inflammation with sudden episodes of fever and severe elevation of acute phase reactants and specific clinical manifestations. |
| What is FMF? | Recurrent polyserositis, brief recurrent episodes of peritonitis, pleuritis, and arthritis, fever, occurs within families, medditerranean, genetic testing needed |
| How is etiology of FMF? | Recessive genetic disease missense and non sense mutations of MEFV gene in short arm of chrm 16, codes for pyrin/marenostrin protein, more than 310 sequence variants in MEFV gene has been identified no all disease phenotype, Homo M694V (valine for methionine) experience more severe disease and develop amyloidosis, V726A (alanine for valine) lower risk of amyloidosis. |
| How is pathophysiology of FMF? | Pyrin is expressed mostly in neutrophils, involved in innate immunity such as inflammasome, asseblage and sensing intracellular danger signals, activating mediators of inflammation, resolving inflammation by autophagy of regulators of innate immunity.
Uninhibited pyrin leads to uncontrolled production of IL1, persistent subclinical inflammation |
| How is epidemiology of FMF? | In Ashkenazi, Sephardic jews, Armenian, Turkish,
Men: Women 2:1
Onset 50-60% before age 10, 80-95% before age 20 |
| How is M&M of FMF? | Nephrotic syndrome (before intiuition of cholchicine therapy mortality due to it was atmost at age 50 years.
Appendectomies (severe peritoneal episodes seemed to indicate appendicitis which caused pt to get appendectomy)
Chronic arthritis (5% of pt sometimes lead to destructive arthritis of hips/knees and may necissate joint replacement)
10% pt with chronic arthritis develop seronegative SpA.
Fertility and pregnancy (1/3 females are infertile, 20-30% get fetal loss pregnancy) |
| How is hx of pt with FMF? | Paroxysms 48-96 hours peak intensity at 12 hours, resolution slower than onset, person's temp rises to 38-40C.
Peritoneum (abdominal pain to peritonitis, constipation with attack and diarrhea with resolve, adhesions are rare)
Pleural and Pericardial (25-80% pleural episodes, effusion, pericarditis but no tamponade (rare))
Synovial Symptoms (25-75% of cases, resemble gout, knees, ankles and wrists most affected, last several days longer than abdorminal symptoms can be protracted, normal joints between attacks, permenant damage unusual, may be only arthritis)
Dermato (50% erysipelaslike rashes in LL below knee)
Muscle (myalgia 3-6 weeks, like fibromyalgia no response to colchicine)
Pelvic (PID in women)
Scrotal attacks (tunica vaginalis inflammation like torsion)
Vasculitis (Purpura and polyarteritis nodosa in children and Behjet)
Amyloidosis (proteinuria following nephrotic syndrome, renal vein thrombosis 30%, increase risk with recurrent arthritis active SAA |
| How is PE of pt with FMF? | Temp high to 40C w/in 12 hours, peritonitis surgical abdomen, splenomegaly, shallow breath and chest tenderness if lung involved, typical joint inflammation, rash well-demarcated erythematous warm under the knee 15-50cm, myalgia, unilateral inflammation of scrotum, Behjet and Henoch-Schonlein, amyloidosis asymptomatic, renal veinthrombosis may be loin pain. |
| How is workup of FMF? | Labs, during attacks see CRP,ESR,SAA,fibrinogen, WBC high, proteinuria in case of amyloidosis, synovial fluid inflammatory
Genetic testing (Dx is clinical but can be supported by genetic testing, two common mutated alleles especially M694V mutation [early onset and close followup] or position 680 to 694 exon 10 more severe.
E148Q common unknown pathgenic significance , not dx of FMF) |
