Skip to main content
Top
Published in: Orphanet Journal of Rare Diseases 1/2014

Open Access 01-12-2014 | Research

Colchicine-free remission in familial Mediterranean fever: featuring a unique subset of the disease-a case control study

Authors: Ilan Ben-Zvi, Tami Krichely-Vachdi, Olga Feld, Merav Lidar, Shaye Kivity, Avi Livneh

Published in: Orphanet Journal of Rare Diseases | Issue 1/2014

Login to get access

Abstract

Background

To demonstrate and clinically, genetically and demographically characterize familial Mediterranean fever (FMF) patients, maintaining remission despite colchicine abstinence.

Methods

FMF patients were screened for an endurance of prolonged remission (≥ 3 years), despite refraining from colchicine. Clinical, demographic and genetic parameters were collected. Data were compared with those of consecutive control FMF subjects, coming to the clinic for their periodic follow up examination.

Results

Of 1000 patients screened over 5 years, 33 manifested colchicine-free remission. The mean duration of the remission period was 12.6 ± 8.1 years. Patients in the remission group had milder severity of FMF, compared to the control group (22 vs. 11 patients with mild disease, respectively, p = 0.003) and a longer diagnosis delay (21 ± 15.7 vs. 13.4 ± 13.5 years, respectively, p = 0.04). Patients experiencing remission suffered mostly of abdominal attacks, low rate of attacks in other sites and low rate of chronic and non-attack manifestations. When the disease resumed activity, it responded well to colchicine, despite using a lower dose, as compared to the control subjects (p < 0.001). None of the patients in this group was homozygous for the M694V mutation (p = 0.0008).

Conclusions

Prolonged colchicine-free remission defines a rare and milder form of FMF with unique clinical, demographic, and molecular characteristics.
Appendix
Available only for authorised users
Literature
1.
go back to reference Ben-Zvi I, Livneh A: Chronic inflammation in FMF: markers, risk factors, outcomes and therapy. Nat Rev Rheumatol. 2010, 2011: 9- Ben-Zvi I, Livneh A: Chronic inflammation in FMF: markers, risk factors, outcomes and therapy. Nat Rev Rheumatol. 2010, 2011: 9-
2.
go back to reference A candidate gene for familial Mediterranean fever. Nat Genet. 1997, 17 (1): 25-31. A candidate gene for familial Mediterranean fever. Nat Genet. 1997, 17 (1): 25-31.
3.
go back to reference Ancient missense mutations in a new member of the RoRet gene family are likely to cause familial Mediterranean fever. The international FMF consortium. Cell. 1997, 90 (4): 797-807. 10.1016/S0092-8674(00)80539-5. Ancient missense mutations in a new member of the RoRet gene family are likely to cause familial Mediterranean fever. The international FMF consortium. Cell. 1997, 90 (4): 797-807. 10.1016/S0092-8674(00)80539-5.
4.
go back to reference Stojanov S, Kastner DL: Familial autoinflammatory diseases: genetics, pathogenesis and treatment. Curr Opin Rheumatol. 2005, 17 (5): 586-599. 10.1097/bor.0000174210.78449.6b.CrossRefPubMed Stojanov S, Kastner DL: Familial autoinflammatory diseases: genetics, pathogenesis and treatment. Curr Opin Rheumatol. 2005, 17 (5): 586-599. 10.1097/bor.0000174210.78449.6b.CrossRefPubMed
5.
go back to reference Touitou I, Lesage S, McDermott M, Cuisset L, Hoffman H, Dode C: Infevers: an evolving mutation database for auto-inflammatory syndromes. Hum Mutat. 2004, 24 (3): 194-198. 10.1002/humu.20080.CrossRefPubMed Touitou I, Lesage S, McDermott M, Cuisset L, Hoffman H, Dode C: Infevers: an evolving mutation database for auto-inflammatory syndromes. Hum Mutat. 2004, 24 (3): 194-198. 10.1002/humu.20080.CrossRefPubMed
6.
go back to reference Piram M, Frenkel J, Gattorno M, Ozen S, Lachmann HJ, Goldbach-Mansky R: A preliminary score for the assessment of disease activity in hereditary recurrent fevers: results from the AIDAI (auto-inflammatory diseases activity index) consensus conference. Ann Rheum Dis. 2011, 70 (2): 309-314. 10.1136/ard.2010.132613.CrossRefPubMedPubMedCentral Piram M, Frenkel J, Gattorno M, Ozen S, Lachmann HJ, Goldbach-Mansky R: A preliminary score for the assessment of disease activity in hereditary recurrent fevers: results from the AIDAI (auto-inflammatory diseases activity index) consensus conference. Ann Rheum Dis. 2011, 70 (2): 309-314. 10.1136/ard.2010.132613.CrossRefPubMedPubMedCentral
7.
go back to reference Mor A, Shinar Y, Zaks N, Langevitz P, Chetrit A, Shtrasburg S: Evaluation of disease severity in familial Mediterranean fever. Semin Arthritis Rheum. 2005, 35 (1): 57-64. 10.1016/j.semarthrit.2005.02.002.CrossRefPubMed Mor A, Shinar Y, Zaks N, Langevitz P, Chetrit A, Shtrasburg S: Evaluation of disease severity in familial Mediterranean fever. Semin Arthritis Rheum. 2005, 35 (1): 57-64. 10.1016/j.semarthrit.2005.02.002.CrossRefPubMed
8.
go back to reference Gershoni-Baruch R, Brik R, Zacks N, Shinawi M, Lidar M, Livneh A: The contribution of genotypes at the MEFV and SAA1 loci to amyloidosis and disease severity in patients with familial Mediterranean fever. Arthritis Rheum. 2003, 48 (4): 1149-1155. 10.1002/art.10944.CrossRefPubMed Gershoni-Baruch R, Brik R, Zacks N, Shinawi M, Lidar M, Livneh A: The contribution of genotypes at the MEFV and SAA1 loci to amyloidosis and disease severity in patients with familial Mediterranean fever. Arthritis Rheum. 2003, 48 (4): 1149-1155. 10.1002/art.10944.CrossRefPubMed
9.
go back to reference Livneh A, Langevitz P, Zemer D, Zaks N, Kees S, Lidar T: Criteria for the diagnosis of familial Mediterranean fever. Arthritis Rheum. 1997, 40 (10): 1879-1885. 10.1002/art.1780401023.CrossRefPubMed Livneh A, Langevitz P, Zemer D, Zaks N, Kees S, Lidar T: Criteria for the diagnosis of familial Mediterranean fever. Arthritis Rheum. 1997, 40 (10): 1879-1885. 10.1002/art.1780401023.CrossRefPubMed
10.
go back to reference Kogan A, Shinar Y, Lidar M, Revivo A, Langevitz P, Padeh S: Common MEFV mutations among Jewish ethnic groups in Israel: high frequency of carrier and phenotype III states and absence of a perceptible biological advantage for the carrier state. Am J Med Genet. 2001, 102 (3): 272-276. 10.1002/ajmg.1438.CrossRefPubMed Kogan A, Shinar Y, Lidar M, Revivo A, Langevitz P, Padeh S: Common MEFV mutations among Jewish ethnic groups in Israel: high frequency of carrier and phenotype III states and absence of a perceptible biological advantage for the carrier state. Am J Med Genet. 2001, 102 (3): 272-276. 10.1002/ajmg.1438.CrossRefPubMed
11.
go back to reference Barakat MH, Karnik AM, Majeed HW, el-Sobki NI, Fenech FF: Familial Mediterranean fever (recurrent hereditary polyserositis) in Arabs--a study of 175 patients and review of the literature. Q J Med. 1986, 60 (233): 837-847.PubMed Barakat MH, Karnik AM, Majeed HW, el-Sobki NI, Fenech FF: Familial Mediterranean fever (recurrent hereditary polyserositis) in Arabs--a study of 175 patients and review of the literature. Q J Med. 1986, 60 (233): 837-847.PubMed
12.
go back to reference Schwabe AD, Peters RS: Familial Mediterranean fever in Armenians. Analysis of 100 cases. Med (Baltimore). 1974, 53 (6): 453-462. 10.1097/00005792-197411000-00005.CrossRef Schwabe AD, Peters RS: Familial Mediterranean fever in Armenians. Analysis of 100 cases. Med (Baltimore). 1974, 53 (6): 453-462. 10.1097/00005792-197411000-00005.CrossRef
13.
go back to reference Sohar E, Gafni J, Pras M, Heller H: Familial Mediterranean fever. A survey of 470 cases and review of the literature. Am J Med. 1967, 43 (2): 227-253. 10.1016/0002-9343(67)90167-2.CrossRefPubMed Sohar E, Gafni J, Pras M, Heller H: Familial Mediterranean fever. A survey of 470 cases and review of the literature. Am J Med. 1967, 43 (2): 227-253. 10.1016/0002-9343(67)90167-2.CrossRefPubMed
14.
go back to reference Mimouni A, Magal N, Stoffman N, Shohat T, Minasian A, Krasnov M: Familial Mediterranean fever: effects of genotype and ethnicity on inflammatory attacks and amyloidosis. Pediatrics. 2000, 105 (5): E70-10.1542/peds.105.5.e70.CrossRefPubMed Mimouni A, Magal N, Stoffman N, Shohat T, Minasian A, Krasnov M: Familial Mediterranean fever: effects of genotype and ethnicity on inflammatory attacks and amyloidosis. Pediatrics. 2000, 105 (5): E70-10.1542/peds.105.5.e70.CrossRefPubMed
15.
go back to reference Pras E, Livneh A, Balow JE, Kastner DL, Pras M, Langevitz P: Clinical differences between North African and Iraqi Jews with familial Mediterranean fever. Am J Med Genet. 1998, 75 (2): 216-219. 10.1002/(SICI)1096-8628(19980113)75:2<216::AID-AJMG20>3.0.CO;2-R.CrossRefPubMed Pras E, Livneh A, Balow JE, Kastner DL, Pras M, Langevitz P: Clinical differences between North African and Iraqi Jews with familial Mediterranean fever. Am J Med Genet. 1998, 75 (2): 216-219. 10.1002/(SICI)1096-8628(19980113)75:2<216::AID-AJMG20>3.0.CO;2-R.CrossRefPubMed
16.
go back to reference Shohat M, Magal N, Shohat T, Chen X, Dagan T, Mimouni A: Phenotype-genotype correlation in familial Mediterranean fever: evidence for an association between Met694Val and amyloidosis. Eur J Hum Genet. 1999, 7 (3): 287-292. 10.1038/sj.ejhg.5200303.CrossRefPubMed Shohat M, Magal N, Shohat T, Chen X, Dagan T, Mimouni A: Phenotype-genotype correlation in familial Mediterranean fever: evidence for an association between Met694Val and amyloidosis. Eur J Hum Genet. 1999, 7 (3): 287-292. 10.1038/sj.ejhg.5200303.CrossRefPubMed
17.
go back to reference Ben-Chetrit E, Ben-Chetrit A: Familial Mediterranean fever and menstruation. BJOG. 2001, 108 (4): 403-407.PubMed Ben-Chetrit E, Ben-Chetrit A: Familial Mediterranean fever and menstruation. BJOG. 2001, 108 (4): 403-407.PubMed
18.
go back to reference Stoffman N, Magal N, Shohat T, Lotan R, Koman S, Oron A: Higher than expected carrier rates for familial Mediterranean fever in various Jewish ethnic groups. Eur J Hum Genet. 2000, 8 (4): 307-310. 10.1038/sj.ejhg.5200446.CrossRefPubMed Stoffman N, Magal N, Shohat T, Lotan R, Koman S, Oron A: Higher than expected carrier rates for familial Mediterranean fever in various Jewish ethnic groups. Eur J Hum Genet. 2000, 8 (4): 307-310. 10.1038/sj.ejhg.5200446.CrossRefPubMed
19.
go back to reference Livneh A, Langevitz P, Shinar Y, Zaks N, Kastner DL, Pras M: MEFV mutation analysis in patients suffering from amyloidosis of familial Mediterranean fever. Amyloid. 1999, 6 (1): 1-6. 10.3109/13506129908993281.CrossRefPubMed Livneh A, Langevitz P, Shinar Y, Zaks N, Kastner DL, Pras M: MEFV mutation analysis in patients suffering from amyloidosis of familial Mediterranean fever. Amyloid. 1999, 6 (1): 1-6. 10.3109/13506129908993281.CrossRefPubMed
20.
go back to reference Tamir N, Langevitz P, Zemer D, Pras E, Shinar Y, Padeh S: Late-onset familial Mediterranean fever (FMF): a subset with distinct clinical, demographic, and molecular genetic characteristics. Am J Med Genet. 1999, 87 (1): 30-35. 10.1002/(SICI)1096-8628(19991105)87:1<30::AID-AJMG6>3.0.CO;2-B.CrossRefPubMed Tamir N, Langevitz P, Zemer D, Pras E, Shinar Y, Padeh S: Late-onset familial Mediterranean fever (FMF): a subset with distinct clinical, demographic, and molecular genetic characteristics. Am J Med Genet. 1999, 87 (1): 30-35. 10.1002/(SICI)1096-8628(19991105)87:1<30::AID-AJMG6>3.0.CO;2-B.CrossRefPubMed
Metadata
Title
Colchicine-free remission in familial Mediterranean fever: featuring a unique subset of the disease-a case control study
Authors
Ilan Ben-Zvi
Tami Krichely-Vachdi
Olga Feld
Merav Lidar
Shaye Kivity
Avi Livneh
Publication date
01-12-2014
Publisher
BioMed Central
Published in
Orphanet Journal of Rare Diseases / Issue 1/2014
Electronic ISSN: 1750-1172
DOI
https://doi.org/10.1186/1750-1172-9-3

Other articles of this Issue 1/2014

Orphanet Journal of Rare Diseases 1/2014 Go to the issue