familial Mediterranean fever (FMF, recurrent polyserositis)
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Introduction
Recurrent systemic inflammatory disorder.
Etiology
Epidemiology
(prevalence in parenthesis)
- ethnic groups from the easterm Mediterranean basin
- Sephardic Jewish (0.1-0.4%)
- Ashkenazi Jewish (0.001%)
- Armenian (0.2%)
- Arabs (0.1%)
- Turkish (0.04%)
- male:female ratio is 1.5-2.0: 1
- generally presents during childhood or adolescence
- 65% < 10 years of age
- 90% < 20 years of age
Pathology
- amyloidosis (if untreated)
- amyloid protein SAA produced as acute phase reactant deposits as amyloid protein AA in tissues
- kidney (renal failure)
- adrenal gland (adrenal failure)
- autosomal dominant form is resistant to colchicine thus prone to AA amyloidosis
- mortality from tuberculosis may be attenuated[4]
Genetics
- autosomal recessive & autosomal dominant inheritance
- autosomal dominant form is resistant to colchicine
- disease maps to chromosome 16p
- mutation in pyrin gene (MEFV)
- most mutations in exon 10 aa 680-761
- M694V Met694 -> Val694 homozygotes may have most severe form of disease
- mutation in pyrin gene (MEFV)
Clinical manifestations
- recurrent symptoms
- most episodes last 12-72 hours
- symptoms generally begin in childhood or adolescence
- 10% of cases present in adults[1]
- episodic fever (38-40 C)
- pelvic pain may mimic pelvic inflammatory disease
- abdominal pain
- chest pain
- nausea
- serositis
- peritonitis may be purulent but sterile[13]
- pleuritis: pleural effusion may occur
- pericarditis
- inflammation of the tunica vaginalis testis may mimic testicular torsion
- arthritis (asymmetric) monoarthritis
- myalgias not responsive to colchicine
- may resemble fibromyalgia
- rash (50% of patients)
- may occur as only manifestation other than fever
- generally occurs on legs, especially below the knee
- may resemble erysipelas or cellulitis
- meningitis
Laboratory
- urinalysis
- proteinuria
- hematuria occurs in 5%
- serum amyloid A (AA amyloid) is positive[1]
- routine blood tests during acute attack are non-specific
- complete blood count (CBC) may show leukocytosis with a predominance of neutrophils
- serum C-reactive protein generally elevated
- erythrocyte sedimentation rate (ESR) generally elevated
- plasma fibrinogen may be elevated[13]
- joint aspiration reveals inflammatory (purulent) joint
- DNA testing: FMF Strip Assay, Pronto FMF[8]
Radiology
non-specifc findings
Complications
- misdiagnosis as surgical abdomen
- death from nephrotic syndrome by age 50 if untreated
- lower than expected incidence of cancer*[11]
- cancer incidence lower than expected in both men & women (RR=0.66 & 0.75)
- vasculitis (increased frequency)
* excluding nonmelanoma skin cancer
Differential diagnosis
- rheumatic fever
- appendicitis
- pseudogout
- Lyme disease
- nephrolithiasis
- pericarditis
- pleurodynia
- lupus erythematosus
- erysipelas or cellulitis
- familial hibernian fever; TNF receptor-associated periodic syndrome (TRAPS)
- febrile episodes generally last 7-21 days
- conjunctivitis & periorbital edema[13]
Management
- episodes of synovitis & serositis
- daily oral colchicine
- 0.6 mg PO BID
- effective in preventing flares & AA amyloidosis[1]
- autosomal dominant form is resistant to colchicine
- etanercept, canakinumab[12] or anakinra[1] may be useful in patients not responding to colchicine
- joint replacement is rarely needed
- life expectancy is related to effects of amyloidosis
- consultation with nephrologist &/or rheumatologist as indicated
More general terms
Additional terms
References
- ↑ 1.0 1.1 1.2 1.3 1.4 Medical Knowledge Self Assessment Program (MKSAP) 11,14,16,17,18. American College of Physicians, Philadelphia 1998,2006,2012,2015,2018.
- ↑ Ben-Cherit E, Levy M Familial Mediterranean fever. Lancet 351:659, 1998 PMID: https://www.ncbi.nlm.nih.gov/pubmed/9500348
- ↑ Levneh A et al, Criteria for the diagnosis of familial Mediterranean fever. Arthritis Rheum 40:1879, 1997 PMID: https://www.ncbi.nlm.nih.gov/pubmed/9336425
- ↑ 4.0 4.1 Tunca M, Ben-Chetrit E Familial Mediterranean fever in 2003. Pathogenesis and management.. Clin Exp Rheumatol 21:S53, 2003 PMID: https://www.ncbi.nlm.nih.gov/pubmed/14727461
- ↑ 5.0 5.1 Atagunduz P et al, MEFV mutations are increased in Behcet's disease (BD) and are associated with vascular involvement. Exp Rheumatol 21:S35, 2003 PMID: https://www.ncbi.nlm.nih.gov/pubmed/14727457
- ↑ Mor A et al, Abdominal and digestive system associations of familial Mediterranean fever. Am J Gastroenterol 98:2594, 2003 PMID: https://www.ncbi.nlm.nih.gov/pubmed/14687803
- ↑ 7.0 7.1 Gershoni-Baruch R et al, Prevalence and significance of mutations in the familial Mediterranean fever gene in Henoch-Schonlein purpura. J Pediatr 143:658, 2003 PMID: https://www.ncbi.nlm.nih.gov/pubmed/14615741
- ↑ 8.0 8.1 Touitou I, Standardized testing for mutations in familial Mediterranean fever. Clin Chem 49:1781, 2003 PMID: https://www.ncbi.nlm.nih.gov/pubmed/14578308
Oberkanins C et al, Genetic testing for familial Mediterranean fever in Austria by means of reverse-hybridization teststrips. Clin Chem. 2003 Nov;49(11):1948-50 PMID: https://www.ncbi.nlm.nih.gov/pubmed/14578333
Tchernitchko D et al, Clinical evaluation of a reverse hybridization assay for the molecular detection of twelve MEFV gene mutations. Clin Chem 49:1942, 2003 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/14578331 - ↑ <Internet> http://www.emedicine.com/med/topic1410.htm has an excellent discussion
- ↑ Ben-Chetrit E, Touitou I. Familial mediterranean Fever in the world. Arthritis Rheum. 2009 Oct 15;61(10):1447-53 PMID: https://www.ncbi.nlm.nih.gov/pubmed/19790133
- ↑ 11.0 11.1 Brenner R, Ben-Zvi I, Shinar Y et al. Familial Mediterranean fever and incidence of cancer. Arthritis Rheumatol 2018 Jan; 70:127 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/28992365 <Internet> http://onlinelibrary.wiley.com/doi/10.1002/art.40344/abstract
- ↑ 12.0 12.1 De Benedetti F, Gattorno M, Anton J et al Canakinumab for the Treatment of Autoinflammatory Recurrent Fever Syndromes. N Engl J Med 2018; 378:1908-1919. May 17, 2018 PMID: https://www.ncbi.nlm.nih.gov/pubmed/29768139 https://www.nejm.org/doi/full/10.1056/NEJMoa1706314
- ↑ 13.0 13.1 13.2 13.3 NEJM Knowledge+ Complex Medical Care
- ↑ Mediterranean fever, familial http://ghr.nlm.nih.gov/condition=mediterraneanfeverfamilial
Patient information
familial Mediterranean fever patient information