Familial mediterranean fever natural history, complications and prognosis

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sahar Memar Montazerin, M.D.[2]

Overview

Common complications of familial Mediterranean fever include amyloidosis and increased risk of vasculitic disorders. The prognosis does not differ from that of the general population. However, renal involvement is the determinant factor of patient survival rate.

Natural History, Complications, and Prognosis

Natural History

The symptoms of familial Mediterranean fever usually develop in the first two decades of life and start with symptoms such as fever and serositis.^[1]
Serositis manifests with abdominal pain, and/or chest pain, arthralgia and/or arthritis of the hip, knee or ankle, and erysiplas-like erythema, frequently on the lower limbs.^[2]
Fever episodes may last 1 to 3 days.
Patients usually manifest minimal symptoms in between the attacks.
Even i the same patient, clinical presentation may vary over time.
If left untreated, 75% of patients with familial Mediterranean fever may progress to develop amyloidosis.^[3]

Complications

The most devastating complication of FMF is the development of AA-amyloidosis which may lead to end-stage renal disease.^[4]^[5]

The development of amyloidosis has been associated with the following factors:
- Particular MEFV mutations (M694V, M694I, or M680I)
- Family history of amyloidosis
- Male sex

FMF may also be complicated with non-amyloid kidney disease such as:^[6]^[7]

Other complications of FMF include:

Emergency surgery (usually due to confusion with an acute abdomen of other cause).^[10]
Band adhesion which may lead to bowel obstruction, pelvic pain, and reduced fertility.^[11]
Arthritis^[12]

Prognosis

Prognosis is generally excellent. However, amyloid renal involvement is the determinant factor of patient survival rate.^[4]

References

↑ Sohar E, Gafni J, Pras M, Heller H (August 1967). “Familial Mediterranean fever. A survey of 470 cases and review of the literature”. Am. J. Med. 43 (2): 227–53. PMID 5340644.
↑ Lidar M, Yaqubov M, Zaks N, Ben-Horin S, Langevitz P, Livneh A (June 2006). “The prodrome: a prominent yet overlooked pre-attack manifestation of familial Mediterranean fever”. J. Rheumatol. 33 (6): 1089–92. PMID 16755655.
↑ Gafni J, Ravid M, Sohar E (1968). “The role of amyloidosis in familial mediterranean fever. A population study”. Isr. J. Med. Sci. 4 (5): 995–9. PMID 5715490.
↑ ^4.0 ^4.1 Akar S, Yuksel F, Tunca M, Soysal O, Solmaz D, Gerdan V, Celik A, Sen G, Onen F, Akkoc N (May 2012). “Familial Mediterranean fever: risk factors, causes of death, and prognosis in the colchicine era”. Medicine (Baltimore). 91 (3): 131–6. doi:10.1097/MD.0b013e3182561a45. PMID 22543627.
↑ Lachmann, Helen J. (2015). “Long-Term Complications of Familial Mediterranean Fever”. 3: 91–105. doi:10.1007/978-3-319-14615-7_6. ISSN 2282-6505.
↑ Kukuy O, Livneh A, Ben-David A, Kopolovic J, Volkov A, Shinar Y, Holtzman E, Dinour D, Ben-Zvi I (December 2013). “Familial Mediterranean fever (FMF) with proteinuria: clinical features, histology, predictors, and prognosis in a cohort of 25 patients”. J. Rheumatol. 40 (12): 2083–7. doi:10.3899/jrheum.130520. PMID 24128782.
↑ Ardalan M, Nasri H (November 2014). “Massive proteinuria and acute glomerulonephritis picture in a patient with Familial Mediterranean fever and E148Q mutation”. Iran J Kidney Dis. 8 (6): 486–8. PMID 25362225.
↑ Rigante, Donato; Federico, Gilda; Ferrara, Pietro; Maggiano, Nicola; Avallone, Laura; Pugliese, Anna Lisa; Stabile, Achille (2005). “IgA nephropathy in an Italian child with familial Mediterranean fever”. Pediatric Nephrology. 20 (11): 1642–1644. doi:10.1007/s00467-005-2023-5. ISSN 0931-041X.
↑ Cagdas, Deniz N.; Gucer, Safak; Kale, Gülsev; Duzova, Ali; Ozen, Seza (2005). “Familial Mediterranean fever and mesangial proliferative glomerulonephritis: report of a case and review of the literature”. Pediatric Nephrology. 20 (9): 1352–1354. doi:10.1007/s00467-005-1991-9. ISSN 0931-041X.
↑ Samli H, Içduygu FM, Ozgöz A, Akbulut G, Hekimler K, Imirzalioglu N (2009). “Surgery for acute abdomen and MEFV mutations in patients with FMF”. Acta Reumatol Port. 34 (3): 520–4. PMID 19820675.
↑ Ciftci AO, Tanyel FC, Büyükpamukçu N, Hiçsönmez A (April 1995). “Adhesive small bowel obstruction caused by familial Mediterranean fever: the incidence and outcome”. J. Pediatr. Surg. 30 (4): 577–9. PMID 7595838.
↑ Moradian, Mike M.; Sarkisian, Tamara; Amaryan, Gayane; Hayrapetyan, Hasmik; Yeghiazaryan, Anna; Davidian, Nairi; Avanesian, Nare (2013). “Patient management and the association of less common familial Mediterranean fever symptoms with other disorders”. Genetics in Medicine. 16 (3): 258–263. doi:10.1038/gim.2013.112. ISSN 1098-3600.

[pmid5340644-1] Sohar E, Gafni J, Pras M, Heller H (August 1967). “Familial Mediterranean fever. A survey of 470 cases and review of the literature”. Am. J. Med. 43 (2): 227–53. PMID 5340644.

[pmid16755655-2] Lidar M, Yaqubov M, Zaks N, Ben-Horin S, Langevitz P, Livneh A (June 2006). “The prodrome: a prominent yet overlooked pre-attack manifestation of familial Mediterranean fever”. J. Rheumatol. 33 (6): 1089–92. PMID 16755655.

[pmid5715490-3] Gafni J, Ravid M, Sohar E (1968). “The role of amyloidosis in familial mediterranean fever. A population study”. Isr. J. Med. Sci. 4 (5): 995–9. PMID 5715490.

[pmid22543627-4] 4.0 ^4.1 Akar S, Yuksel F, Tunca M, Soysal O, Solmaz D, Gerdan V, Celik A, Sen G, Onen F, Akkoc N (May 2012). “Familial Mediterranean fever: risk factors, causes of death, and prognosis in the colchicine era”. Medicine (Baltimore). 91 (3): 131–6. doi:10.1097/MD.0b013e3182561a45. PMID 22543627.

[Lachmann2015-5] Lachmann, Helen J. (2015). “Long-Term Complications of Familial Mediterranean Fever”. 3: 91–105. doi:10.1007/978-3-319-14615-7_6. ISSN 2282-6505.

[pmid24128782-6] Kukuy O, Livneh A, Ben-David A, Kopolovic J, Volkov A, Shinar Y, Holtzman E, Dinour D, Ben-Zvi I (December 2013). “Familial Mediterranean fever (FMF) with proteinuria: clinical features, histology, predictors, and prognosis in a cohort of 25 patients”. J. Rheumatol. 40 (12): 2083–7. doi:10.3899/jrheum.130520. PMID 24128782.

[7] Ardalan M, Nasri H (November 2014). “Massive proteinuria and acute glomerulonephritis picture in a patient with Familial Mediterranean fever and E148Q mutation”. Iran J Kidney Dis. 8 (6): 486–8. PMID 25362225.

[RiganteFederico2005-8] Rigante, Donato; Federico, Gilda; Ferrara, Pietro; Maggiano, Nicola; Avallone, Laura; Pugliese, Anna Lisa; Stabile, Achille (2005). “IgA nephropathy in an Italian child with familial Mediterranean fever”. Pediatric Nephrology. 20 (11): 1642–1644. doi:10.1007/s00467-005-2023-5. ISSN 0931-041X.

[CagdasGucer2005-9] Cagdas, Deniz N.; Gucer, Safak; Kale, Gülsev; Duzova, Ali; Ozen, Seza (2005). “Familial Mediterranean fever and mesangial proliferative glomerulonephritis: report of a case and review of the literature”. Pediatric Nephrology. 20 (9): 1352–1354. doi:10.1007/s00467-005-1991-9. ISSN 0931-041X.

[pmid19820675-10] Samli H, Içduygu FM, Ozgöz A, Akbulut G, Hekimler K, Imirzalioglu N (2009). “Surgery for acute abdomen and MEFV mutations in patients with FMF”. Acta Reumatol Port. 34 (3): 520–4. PMID 19820675.

[pmid7595838-11] Ciftci AO, Tanyel FC, Büyükpamukçu N, Hiçsönmez A (April 1995). “Adhesive small bowel obstruction caused by familial Mediterranean fever: the incidence and outcome”. J. Pediatr. Surg. 30 (4): 577–9. PMID 7595838.

[MoradianSarkisian2013-12] Moradian, Mike M.; Sarkisian, Tamara; Amaryan, Gayane; Hayrapetyan, Hasmik; Yeghiazaryan, Anna; Davidian, Nairi; Avanesian, Nare (2013). “Patient management and the association of less common familial Mediterranean fever symptoms with other disorders”. Genetics in Medicine. 16 (3): 258–263. doi:10.1038/gim.2013.112. ISSN 1098-3600.

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