Home About us Current issue Back issues Submission Instructions Advertise Contact Login   

Search Article 
  
Advanced search 
 
Saudi Journal of Kidney Diseases and Transplantation
Users online: 1431 Home Bookmark this page Print this page Email this page Small font sizeDefault font size Increase font size 
 


 
ARTICLES Table of Contents   
Year : 2003  |  Volume : 14  |  Issue : 3  |  Page : 378-385
Familial Mediterranean fever and Renal Disease


University of Iowa Hospitals and Clinics, Department of Pediatrics, Division of Medical Genetics, USA

Click here for correspondence address and email
 

   Abstract 

Familial Mediterranean Fever (FMF) is a genetic disorder frequently diagnosed among the Arabs. It is also prevalent among Jews, Armenians and Turks. The clinical picture consists of febrile and painful attacks such as joint or chest pain that differ in quality across patients and even within the same patient. The gene responsible for FMF, MEFV, has been cloned and mutations were identified within its coding sequence. It encodes a protein that is expected to be a down regulator of inflammation. The major renal involvement in FMF is the occurrence of amyloidosis that primarily affects the kidneys causing proteinuria and ending in death from renal failure. It can be treated by dialysis and renal transplantation, but can be prevented by a daily regimen of colchicine. Other renal manifestations of FMF are discussed.

Keywords: Familial Mediterranean Fever, Arabs, Abdominal Pain, Colchicine.

How to cite this article:
El-Shanti HI. Familial Mediterranean fever and Renal Disease. Saudi J Kidney Dis Transpl 2003;14:378-85

How to cite this URL:
El-Shanti HI. Familial Mediterranean fever and Renal Disease. Saudi J Kidney Dis Transpl [serial online] 2003 [cited 2019 Jul 16];14:378-85. Available from: http://www.sjkdt.org/text.asp?2003/14/3/378/33017

   Introduction Top


Familial  Mediterranean fever More Details (FMF) was first described as a distinct disease entity, under the name of benign paroxysmal peri­tonitis, in 1945. [1] Although earlier on it had several names, the international medical community in the early sixties adopted the name suggested by the team led by Heller, [2] which reflects on three classical aspects of the disorder. Firstly, Familial, as it is autosomal recessive, [3] though about half of the patients do not have a family history. Secondly, Medi-terranean, as it is prevalent in the Mediterranean populations, namely, Jews (non-Ashkenazi), Armenians, Turks and Arabs. [4],[5],[6],[7],[8],[9],[10],[11] Thirdly, Fever, which is the most common component of the disorder; 12 however, some patients do not realize that they are febrile during the attacks.


   Clinical Picture Top


The clinical picture consists of febrile and painful attacks that are usually of acute onset, variable frequency, mostly without a noticeable triggering factor but often occur­ring with menstruation, emotional stress or strenuous physical activity. [3] The pain is usually severe occurring in the abdomen, chest and joints due to inflammation of the peritoneum, pleura and synovial membrane. The attacks last from 12-72 hours and abort abruptly but the arthralgia may last longer. The attacks start, most commonly, during childhood or adolescence, with about 80% of patients presenting their symptoms before the age of 20 years and very few after theage of 40. [5],[6],[11],[13],[14] The intensity of symptoms and frequency vary from one attack to another and from one patient to another even within the same family. [15] All patients suffer from abdominal pain at one point, and it is reported in 50% of patients as the first symptom. [11] It can be diffuse or locali­zed, ranging in intensity from mild bloating to peritonitis with rigidity and rebound tenderness. There can be constipation and the history may include a laparotomy for appendectomy. [15] Chest pain is present in about 50% of attacks, usually in the form of unilateral pleurisy with diminished breath sounds, friction rub and maybe effusion or collapse. [13] Joint pain is present in about 50-75% of attacks and it is in the form of arthritis or arthralgia. [16] The arthritis is usually monoarticular affecting the knee, hip or ankle joints. [5],[10],[16][17] Some patients deve­lop protracted arthritis, synovitis, muscle atrophy, erosions and juxta-articular osteo­porosis. [16],[18],[19],[20] The most characteristic skin lesion is the erysipelas-like erythema, occur­ring in 3-45% of attacks. [21],[22] It is unilateral or bilateral red, warm, swollen lesions about 10-15 cm in diameter, occurring below the knee or on the dorsum of the foot. [21],[22]

Uncommon manifestations include acute scrotal inflammation, [23],[24],[25] myalgia of variable intensity and duration, [26],[27],[28] meningeal irritation and increased CSF proteins and cells, [29],[30],[31] impaired female fertility, [32] pericarditis, [33] vasculitis, [34] purpuric lesions, [22] and nephro­pathy [35],[36],[37],[38]

The laboratory findings are non-specific and include leukocytosis with left shift, elevated erythrocyte sedimentation rate (ESR), high acute phase reactant titres like C-reactive protein (CRP), serum amyloid A (SAA), fibrinogen, haptoglobin, C3 and C4. [3] There may be transient albuminuria and microsco­pic hematuria. Between attacks, patients are mostly free of symptoms. However, there may be slight discomfort, slight fever, spleno­megaly, anemia, increased fibrinogen and increased immunoglobulin levels. [3]


   Genetics Top


The gene responsible for FMF, then named MEF, was mapped to the short arm of chromosome 16, with clear evidence for genetic homogeneity of the disorder. [39],[40],[41] The gene for FMF, now called MEFV, was cloned by two consortia independently and simultaneously. [42],[43]3 The gene is composed of 10 exons, the cDNA is 3505 nucleotides long and it encodes for a 781 amino-acid long protein called pyrin by the International consortium and marinostrin by the French consortium. [42],[43] Up till now, over 50 different mutations and polymorphisms have been identified, most of them clustered in the 10 th exon of MEFV. [44] However, the five mutations E148Q, M680I, M694V, M694I and V726A described around the time of the cloning of the gene, remain the most common across the major affected populations. [3]


   Renal Manifestations Top


One of the significant impacts of FMF on the affected individuals is the occurrence of amyloidosis, which represents the major renal involvement in FMF. Although amyloidosis can affect other organs, it primarily mani­fests as a nephropathy that passes through consecutive stages of proteinuria, nephrotic syndrome, uremia, end-stage renal failure and death. [45],[46],[47] It is due to the deposition of AA protein, which is a cleavage product of the acute phase reactant SAA by the liver. [48] Chemically, it is the same type of reactive amyloidosis associated with chronic infe­ctions such as tuberculosis, bronchiectasis and rheumatoid arthritis. [49] Amyloid A usually deposits in kidneys, adrenal glands, intestine, spleen, liver, lung, thyroid, heart, stomach and testes. Intestinal malabsorption and adrenal insufficiency became recognizable signs of amyloidosis after the establishment of renal dialysis as a treatment for renal failure and thus the prolongation of the lives of those affected. Amyloidosis due to FMF does not result in a neuropathy or arthro­pathy. [15] Routine urinalysis in search of early albuminuria is imperative in the care of affected individuals, as it appears early in the course of renal involvement. [15] Once the proteinuria is confirmed the diagnosis of amyloidosis must be confirmed by renal biopsy, rectal biopsy, bone marrow biopsy, abdominal fat aspiration or gingival bio­psy [50],[51],[52] The sensitivity of the renal biopsy is 88%, while that of the rectal and bone marrow biopsy is close to 75%. [50],[51] The abdo­minal fat tissue and the gingival biopsies are less sensitive and are not favoured in a diagnostic setting. [50],[52] The biopsy should be stained with congo red and viewed under polarized light where AA gives a characte­ristic apple green colour. [53]

From a clinical perspective, FMF patients are classified into three phenotypes; the classical form being phenotype I. Phenotype II denotes individuals who develop amyloi­dosis without previous painful attacks typical of FMF. [54],[55],[56] Individuals who have the disease genotype but are non-penetrant will have phenotype III. [57] The occurrence of amyloido­sis is independent of the frequency, duration or intensity of the attack, [45] which is further supported by the presence of phenotype II.

Even before the introduction of colchicine, not every patient developed amyloidosis. Family history and consanguinity, as eviden­ced by homozygosity, are major determinants of amyloidosis in FMF. [9] Ethnicity contributes significantly to the risk of developing amyloi­dosis, which might be due to the presence of specific mutations in specific ethnic groups. [49] The frequency is higher in Jews of North African ancestry and in Turks, while it is less common in Arabs. [5],[17],[49],[58],[59] The possibility of an environmental influence in the predispo­sition to amyloidosis in FMF patients is shown by the higher incidence of amyloidosis in Armenians living in Armenia than in those living in the United States, even before the introduction of colchicine. [10]

Several investigators have noticed a cor­relation between the mutation M694V, especially in the homozygous state, and amyloidosis. [56],[60],[61],[62],[63],[64],[65],[66],[67] However, several others could not demonstrate that correlation. [68],[69],[70],[71] It was shown that serum amyloid A1 gene (SAA1) is a modifier for the FMF phenotype with seven fold increase in the risk for amyloidosis in patients with the SAA1 a/a genotype. [72] One study has suggested that there is an association between a common polymorphism in exon 2 (A138G) of the MEFV gene and the development of amyloi­dosis in FMF patients. [73] A recent study showed strong linkage disequilibrium between A138G and M694V and confirmed the strong association of amyloidosis and the SAA1 a/a genotype. [74] The correlation between the genotype and phenotype, specially regarding amyloidosis still remains an enigma. The treatment for amyloidosis is hemodialysis and renal transplantation. Colchicine plays an important role in the prevention of amyloidosis, as well as its reaccumulation in a grafted organ. [75]

In addition to amyloidosis, other renal lesions have been described in patients suffering from FMF. In a series of FMF patients, 13 out of 106 had amyloidosis but 23 had renal lesions other than amyloid. [76] The 23 patients had hematuria, albuminuria and a variety of glomerulonephritides. A number of kidney biopsies showed proliferative glomerulo­nephritis but the immunofluorescent studies were not available then. [76],[77] One report observed 10 episodes of Henoch-Shonlein purpura in eight FMF patients; two of the patients had kidney biopsy which showed focal mesangial proliferative glomerulone­phritis with granular mesangial C3 deposits in one. [78] There is another report of three FMF patients with mesangial IgA deposits of granular pattern with proteinuria, micro­scopic hematuria and high serum IgA level during the painful episodes. [35] There is a report of two patients with biopsy proven rapidly progressive glomerulonephritis type 2 without amyloidosis; both presented with renal failure. [36] There is also a report of three patients with IgM nephropathy in the absence of amyloidosis. [37] A study from Jordan showed that about half of the renal involvement in FMF was non-amyloid. [38]


   Colchicine Top


In the early 70s, two publications intro­duced colchicine as the primary therapy to reduce the frequency of FMF attacks. [79],[80] Its efficacy was established by few placebo­ controlled trials. [81],[82].,[83] A daily regimen of 1-2 mg of oral colchicine, introduced gradually, remains the recommended treatment ever since. [84] It has also been shown to be beneficial for the prevention of amyloidosis in patients before and after renal transplantation. [75],[85],[86],.[87]

While being a miracle therapeutic option for FMF, colchicine is not without its side effects. Many patients suffer from diarrhea and gastrointestinal upset but seem to tolerate it better when it is introduced gradually. [84] In addition, colchicine has been shown to induce lactose intolerance in FMF patients, which can be remedied by a lactose free diet and antiflatulents. [88] Uncommon side effects include myopathy and peripheral neuropathy but mostly in older patients with impaired renal function. [89] To avoid the teratogenic risk of colchicine, it is generally recommended to decrease the colchicine dose, during preg­nancy and to perform amniocentesis early in the second trimester. [84] The concentration of colchicine in breast milk is very low, thus it seems safe for the child during lactation. [84] While oral colchicine has few risks, the intravenous administration of the drug carries major hazards and can lead to multiple organ failure and even death. [90]


   Conclusion Top


The major renal involvement in FMF is the occurrence of amyloidosis. Amyloidosis primarily affects the kidneys causing protei­nuria and ending in death from renal failure. It can be treated by dialysis and renal trans­plantation. Amyloidosis can be prevented in FMF patients with daily colchicine. Colchicine has the benefit of also decreasing the number and intensity of the painful attacks. It is imperative in the care of FMF patients to diagnose amyloidosis early enough to start the appropriate treatment and care.


   Acknowledgement Top


The author is grateful for the support from Jordan University of Science and Technology, Irbid, Jordan (grant # 20020010).

 
   References Top

1.Siegal S. Benign paroxysmal peritonitis. Ann Intern Med 1945; 23:1-21.  Back to cited text no. 1    
2.Sohar E, Pras M, Heller J, Heller H. Genetics of Familial Mediterranean Fever. Arch Intern Med 1961; 107:529-38.  Back to cited text no. 2    
3.El-Shanti HE. Familial Mediterranean Fever. Saudi Med J 2001; 22:104-9.  Back to cited text no. 3    
4.Daniels M, Shohat T, Brenner-Ullman A, Shohat M. Familial Mediterranean fever: high gene frequency among the non-Ashke­nazic and Ashkenazic Jewish populations in Israel. Am J Med Genet 1995; 55:311-4.  Back to cited text no. 4    
5.Barakat MH, Karnik AM, Majeed HW, el­Sobki 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; 60:837-47.  Back to cited text no. 5    
6.Majeed HA, Barakat M. Familial Mediterranean fever (recurrent hereditary polyserositis) in children: analysis of 88 cases. Eur J Pediatr 1989; 148:636-41.  Back to cited text no. 6    
7.Rawashdeh MO, Majeed HA. Familial Mediterranean fever in Arab children: the high prevalence and gene frequency. Eur J Pediatr 1996; 155:540-4.  Back to cited text no. 7    
8.Rogers DB, Shohat M, Petersen GM, et al. Familial Mediterranean fever in Armenians: autosomal recessive inheritance with high gene frequency. Am J Med Genet 1989; 34:168-72.  Back to cited text no. 8    
9.Saatci U, Ozen S, Ozdemir S, et al. Familial Mediterranean fever in children: report of a large series and discussion of the risk and prognostic factors of amyloidosis. Eur J Pediatr 1997; 156:619-23.  Back to cited text no. 9    
10.Schwabe AD, Peters RS. Familial Medite­rranean Fever in Armenians. Analysis of 100 cases. Medicine (Baltimore) 1974; 53:453-62.  Back to cited text no. 10    
11.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; 43:227-53.  Back to cited text no. 11    
12.Majeed HA, Rawashdeh M, Qubain H. Recurrent episodic fever. A presenting feature of familial Mediterranean fever. J Med Liban 1998; 46:12-5.  Back to cited text no. 12    
13.Majeed HA, Rawashdeh M, el-Shanti H, Qubain H, Khuri-Bulos N, Shahin HM. Familial Mediterranean fever in children: the expanded clinical profile. Q J Med 1999; 92:309-18.  Back to cited text no. 13    
14.Rozenbaum M, Rosner I. The clinical features of Familial Mediterranean Fever of elderly onset [letter]. Clin Exp Rheumatol 1994; 12:347-8.  Back to cited text no. 14    
15.Samuels J, Aksentijevich I, Torosyan Y, et al. Familial Mediterranean fever at the millennium. Clinical spectrum, ancient mutations, and a survey of 100 American referrals to the National Institutes of Health. Medicine (Baltimore) 1998; 77:268-97.  Back to cited text no. 15    
16.Majeed HA, Rawashdeh M. The clinical patterns of arthritis in children with familial Mediterranean fever. Q J Med 1997; 90:37-43.  Back to cited text no. 16    
17.Ozer FL, Kaplaman E, Zileli S. Familial Mediterranean fever in Turkey. A report of twenty cases. Am J Med 1971; 50:336-9.  Back to cited text no. 17    
18.Heller H, Gafni J, Michaeli D, et al. The arthritis of familial Mediterranean fever (FMF). Arthritis Rheum 1966; 9:1-17.  Back to cited text no. 18    
19.Sneh E, Pras M, Michaeli D, Shanin N, Gafni J. Protracted arthritis in familial Mediterranean fever. Rheumatol Rehabil 1977; 16:102-6.  Back to cited text no. 19    
20.Yalcinkaya F, Tekin M, Tumer N, Ozkaya N. Protracted arthritis of familial Mediterra­nean fever (an unusual complication). Br J Rheumatol 1997; 36:1228-30.  Back to cited text no. 20    
21.Azizi E, Fisher BK. Cutaneous manifes­tations of familial Mediterranean fever. Arch Dermatol 1976; 112:364-6.  Back to cited text no. 21    
22.Majeed HA, Quabazard Z, Hijazi Z, Farwana S, Harshani F. The cutaneous manifestations in children with familial Mediterranean fever (recurrent hereditary polyserositis). A six-year study. Q J Med 1990; 75:607-16.  Back to cited text no. 22    
23.Eshel G, Vinograd I, Barr J, Zemer D. Acute scrotal pain complicating familial Mediterra­nean fever in children. Br J Surg 1994; 81:894-6.  Back to cited text no. 23    
24.Majeed HA, Ghandour K, Shahin HM. The acute scrotum in Arab children with familial Mediterranean fever. Pediatr Surg Int 2000; 16:72-4.  Back to cited text no. 24    
25.Moskovitz B, Bolkier M, Nativ O. Acute orchitis in recurrent polyserositis. J Pediatr Surg 1995; 30:1517-8.  Back to cited text no. 25    
26.Majeed HA, Al-Qudah AK, Qubain H, Shahin HM. The clinical patterns of myalgia in children with familial Mediterranean fever. Semin Arthritis Rheum 2000; 30:138-43.  Back to cited text no. 26    
27.Langevitz P, Zemer D, Livneh A, Shemer J, Pras M. Protracted febrile myalgia in patients with familial Mediterranean fever. J Rheumatol 1994; 21:1708-9.  Back to cited text no. 27    
28.Langevitz P, Buskila D, Finkelstein R, et al. Fibromyalgia in familial Mediterranean fever. J Rheumatol 1994; 21:1335-7.  Back to cited text no. 28    
29.Barakat MH, Mustafa HT, Shakir RA. Mollaret's meningitis. A variant of recurrent hereditary polyserositis, both provoked by metaraminol. Arch Neurol 1988; 45:926-7.  Back to cited text no. 29    
30.Gedalia A, Zamir S. Neurologic manifes­tations in familial Mediterranean fever. Pediatr Neurol 1993; 9:301-2.  Back to cited text no. 30    
31.Schwabe AD, Monroe JB. Meningitis in familial Mediterranean fever. Am J Med 1988; 85:715-7.  Back to cited text no. 31    
32.Ehrenfeld M, Brzezinski A, Levy M, Eliakim M. Fertility and obstetric history in patients with familial Mediterranean fever on long-term colchicine therapy. Br J Obstet Gynaecol 1987; 94:1186-91.  Back to cited text no. 32    
33.Kees S, Langevitz P, Zemer D, Padeh S, Pras M, Livneh A. Attacks of pericarditis as a manifestation of familial Mediterranean fever (FMF). Q J Med 1997; 90:643-7.  Back to cited text no. 33    
34.Ozdogan H, Arisoy N, Kasapcapur O, et al. Vasculitis in familial Mediterranean fever. J Rheumatol 1997; 24:323-7.  Back to cited text no. 34    
35.Said R, Nasrallah N, Hamzah Y, Tarawneh M, al-Khatib M. IgA nephropathy in patients with familial Mediterranean fever. Am J Nephrol 1988; 8:417-20.  Back to cited text no. 35    
36.Said R, Hamzeh Y, Tarawneh M, el­Khateeb M, Abdeen M, Shaheen A. Rapid progressive glomerulonephritis in patients with familial Mediterranean fever. Am J Kidney Dis 1989; 14:412-6.  Back to cited text no. 36    
37.Said R, Hamzeh Y. IgM nephropathy associated with familial Mediterranean fever. Clin Nephrol 1990; 33:227-31.  Back to cited text no. 37    
38.Said R, Hamzeh Y, Said S, Tarawneh M, al­Khateeb M. Spectrum of renal involvement in familial Mediterranean fever. Kidney Int 1992; 41:414-9.  Back to cited text no. 38    
39.Shohat M, Bu X, Shohat T, et al. The gene for familial Mediterranean fever in both Armenians and non- Ashkenazi Jews is linked to the alpha-globin complex on 16p: evidence for locus homogeneity. Am J Hum Genet 1992; 51:1349-54.  Back to cited text no. 39    
40.Pras E, Aksentijevich I, Gruberg L, et al. Mapping of a gene causing familial Medite­rranean fever to the short arm of chromosome 16. N Engl J Med 1992; 326:1509-13.  Back to cited text no. 40    
41.Pras E, Aksentijevich I, Levy E, et al. The gene causing familial Mediterranean fever maps to the short arm of chromosome 16 in Druze and Moslem Arab families. Hum Genet 1994; 94:576-7.  Back to cited text no. 41    
42.The International FMF Consortium. Ancient missense mutations in a new member of the RoRet gene family are likely to cause familial Mediterranean fever. Cell 1997; 90:797-807.  Back to cited text no. 42    
43.A candidate gene for familial Mediterranean fever. The French FMF Consortium. Nat Genet 1997; 17:25-31.  Back to cited text no. 43    
44.Touitou I. The spectrum of Familial Medite­rranean Fever (FMF) mutations. Eur J Hum Genet 2001; 9:473-83.  Back to cited text no. 44    
45.Heller H, Sohar E, Gafni J, Heller J. Amyloidosis in familial Mediterranean fever. Arch Intern Med 1961; 107:539-50.  Back to cited text no. 45    
46.Lender M. Heredofamilial amyloidosis: incidence in familial Mediterranean fever: A report of two families. Am J Med Sci 1974; 268:291-4.  Back to cited text no. 46    
47.Lender M, Rosenblueth M. Amyloidosis of the kidneys. Review of patients and literature. S Afr Med J 1975; 49:813-7.  Back to cited text no. 47    
48.Pras M, Zaretzky J, Frangione B, Franklin EC. AA protein in a case of "primary" or "idiopathic" amyloidosis. Am J Med 1980; 68:291-4.  Back to cited text no. 48    
49.Pras M, Bronshpigel N, Zemer D, Gafni J. Variable incidence of amyloidosis in familial Mediterranean fever among different ethnic groups. Johns Hopkins Med J 1982; 150:22-6.  Back to cited text no. 49    
50.Blum A, Sohar E. The diagnosis of amyloidosis. Ancillary procedures. Lancet 1962; 1:721-4.  Back to cited text no. 50    
51.Sungur C, Sungur A, Ruacan S, et al. Diagnostic value of bone marrow biopsy in patients with renal disease secondary to familial Mediterranean fever. Kidney Int 1993; 44:834-6.  Back to cited text no. 51    
52.Tishler M, Pras M, Yaron M. Abdominal fat tissue aspirate in amyloidosis of familial Mediterranean fever. Clin Exp Rheumatol 1988; 6:395-7.  Back to cited text no. 52    
53.Wolman M. Amyloid, its nature and molecular structure. Comparison of a new toluidine blue polarized light method with traditional procedures. Lab Invest 1971; 25:104-10.  Back to cited text no. 53    
54.Tinaztepe K, Gucer S, Bakkaloglu A, Tinaztepe B. The association between Henoch-Schonlein syndrome and renal amyloidosis: a proposal of a pathogenic mechanism. Turk J Pediatr 1993; 35:249-56.  Back to cited text no. 54    
55.Saatci U, Bakkaloglu A, Ozen S, Besbas N. Familial Mediterranean fever and amyloidosis in children. Acta Paediatr 1993; 82:705-6.  Back to cited text no. 55    
56.Livneh A, Langevitz P, Shinar Y, et al. MEFV mutation analysis in patients suffering from amyloidosis of familial Mediterranean fever. Amyloid 1999; 6:1-6.  Back to cited text no. 56    
57.Kogan A, Shinar Y, Lidar M, et al. 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; 102:272-6.  Back to cited text no. 57    
58.Ozdemir AI, Sokmen C. Familial Medite­rranean fever among the Turkish people. Am J Gastroenterol 1969; 51:311-6.  Back to cited text no. 58    
59.Armenian HK. Genetic and environmental factors in the aetiology of familial paroxysmal polyserositis. An analysis of 150 cases from Lebanon. Trop Geogr Med 1982; 34:183-7.  Back to cited text no. 59    
60.Ben-Chetrit E. Genotype-phenotype relation and correlation in familial mediterranean fever. Isr Med Assoc J 2001; 3:838-40.  Back to cited text no. 60    
61.Brik R, Shinawi M, Kepten I, Berant M, Gershoni-Baruch R. Familial Mediterranean fever: clinical and genetic characterization in a mixed pediatric population of Jewish and Arab patients. Pediatrics 1999; 103:e70.  Back to cited text no. 61    
62.Cazeneuve C, Sarkisian T, Pecheux C, et al. MEFV-Gene analysis in armenian patients with Familial Mediterranean fever: diagnostic value and unfavorable renal prognosis of the M694V homozygous genotype-genetic and therapeutic implications. Am J Hum Genet 1999; 65:88-97.  Back to cited text no. 62    
63.Dewalle M, Domingo C, Rozenbaum M, et al. Phenotype-genotype correlation in Jewish patients suffering from familial Mediterranean fever (FMF). Eur J Hum Genet 1998; 6:95-7.  Back to cited text no. 63    
64.Majeed HA, El-Shanti H, Al-Khateeb MS, Rabaiha ZA. Genotype/phenotype correlations in Arab patients with familial Mediterranean fever. Semin Arthritis Rheum 2002; 31:371-6.  Back to cited text no. 64    
65.Mansour I, Delague V, Cazeneuve C, et al. Familial Mediterranean fever in Lebanon: mutation spectrum, evidence for cases in Maronites, Greek orthodoxes, Greek catholics, Syriacs and Chiites and for an association between amyloidosis and M694V and M694I mutations. Eur J Hum Genet 2001; 9:51-5.  Back to cited text no. 65    
66.Mimouni A, Magal N, Stoffman N, et al. Familial Mediterranean fever: effects of genotype and ethnicity on inflammatory attacks and amyloidosis. Pediatrics 2000; 105:E70.  Back to cited text no. 66    
67.Shohat M, Magal N, Shohat T, et al. Phenotype-genotype correlation in familial Mediterranean fever: evidence for an asso­ciation between Met694Val and amyloidosis. Eur J Hum Genet 1999; 7:287-92.  Back to cited text no. 67    
68.Akar N, Yalcinkaya F, Akar E, Cakar N. MEFV mutation analysis in Turkish familial Mediterranean fever patients with amyloidosis. Amyloid 1999; 6:301-2.  Back to cited text no. 68    
69.Akar N, Misiroglu M, Yalcinkaya F, et al. MEFV mutations in Turkish patients suffering from Familial Mediterranean Fever. Hum Mutat 2000; 15:118-9.  Back to cited text no. 69    
70.Tekin M, Yalcinkaya F, Cakar N, et al. MEFV mutations in multiplex families with familial Mediterranean fever: is a particular genotype necessary for amyloidosis? Clin Genet 2000; 57:430-4.  Back to cited text no. 70    
71.Yalcinkaya F, Cakar N, Misirlioglu M, et al. Genotype-phenotype correlation in a large group of Turkish patients with familial mediterranean fever: evidence for mutation­independent amyloidosis. Rheumatology (Oxford) 2000; 39:67-72.  Back to cited text no. 71    
72.Cazeneuve C, Ajrapetyan H, Papin S, et al. Identification of MEFV-independent modifying genetic factors for familial Mediterranean fever. Am J Hum Genet 2000; 67:1136-43.  Back to cited text no. 72    
73.Akar E, Yalcinkaya F, Akar N. Is the Ala138Gly alteration of MEFV gene important for amyloidosis? Hum Mutat 2001; 17:71.  Back to cited text no. 73    
74.Altiok O, Seguret F, Touitou I. MEFV sequence variants and amyloidosis: still an enigmatic question. Hum Mutat 2003; 21:96-7.  Back to cited text no. 74    
75.Livneh A, Zemer D, Siegal B, Laor A, Sohar E, Pras M. Colchicine prevents kidney transplant amyloidosis in familial Mediterranean fever. Nephron 1992;60:418-22.  Back to cited text no. 75    
76.Eliakim M. Incidence of amyloidosis in recurrent polyserositis (familial Mediterra­nean fever). Isr J Med Sci 1970; 6:2-8.  Back to cited text no. 76    
77.Eliakim M, Rosenmann E. Renal amyloidosis in a patient with recurrent polyserositis previously manifesting proteinuria with minimal glome­rular changes. Isr J Med Sci 1972; 8:53-6.  Back to cited text no. 77    
78.Flatau E, Kohn D, Schiller D, Lurie M, Levy E. Schonlein-Henoch syndrome in patients with familial Mediterranean fever. Arthritis Rheum 1982; 25:42-7.  Back to cited text no. 78    
79.Ozkan E, Okur O, Ekmekci A, Ozcan R, Tag T. A new approach to the treatment of periodic fever. Med Bull Istanbul 1972;5:44-9.  Back to cited text no. 79    
80.Goldfinger SE. Colchicine for familial Mediterranean fever. N Engl J Med 1972; 287:1302.  Back to cited text no. 80    
81.Goldstein RC, Schwabe AD. Prophylactic colchicine therapy in familial Medite­rranean fever. A controlled, double-blind study. Ann Intern Med 1974; 81:792-4.  Back to cited text no. 81    
82.Dinarello CA, Wolff SM, Goldfinger SE, Dale DC, Alling DW. Colchicine therapy for familial mediterranean fever. A double­blind trial. N Engl J Med 1974; 291:934-7.  Back to cited text no. 82    
83.Zemer D, Revach M, Pras M, et al. A controlled trial of colchicine in preventing attacks of familial mediterranean fever. N Engl J Med 1974; 291:932-4.  Back to cited text no. 83    
84.Ben-Chetrit E, Levy M. Colchicine: 1998 update. Semin Arthritis Rheum 1998;28:48-59.  Back to cited text no. 84    
85.Livneh A, Zemer D, Langevitz P, Laor A, Sohar E, Pras M. Colchicine treatment of AA amyloidosis of familial Mediterranean fever. An analysis of factors affecting out­come. Arthritis Rheum 1994; 37:1804-11.  Back to cited text no. 85    
86.Zemer D, Pras M, Sohar E, Modan M, Cabili S, Gafni J. Colchicine in the prevention and treatment of the amyloidosis of familial Mediterranean fever. N Engl J Med 1986; 314:1001-5.  Back to cited text no. 86    
87.Zemer D, Livneh A, Langevitz P. Reversal of the nephrotic syndrome by colchicine in amyloidosis of familial Mediterranean fever. Ann Intern Med 1992; 116:426.  Back to cited text no. 87    
88.Fradkin A, Yahav J, Zemer D, Jonas A. Colchicine-induced lactose malabsorption in patients with familial Mediterranean fever. Isr J Med Sci 1995; 31:616-20.  Back to cited text no. 88    
89.Kuncl RW, Duncan G, Watson D, Alderson K, Rogawski MA, Peper M. Colchicine myopathy and neuropathy. N Engl J Med 1987; 316:1562-8.  Back to cited text no. 89    
90.Wallace SL, Singer JZ. Review: systemic toxicity associated with the intravenous administration of colchicine-guidelines for use. J Rheumatol 1988; 15:495-9.  Back to cited text no. 90    

Top
Correspondence Address:
Hatem I El-Shanti
University of Iowa Hospitals and Clinics, 2615 JCP, 200 Hawkins Drive, Iowa City, Iowa, 52242
USA
Login to access the Email id


PMID: 17657110

Rights and Permissions




 

Top
 
 
    Similar in PUBMED
    Search Pubmed for
    Search in Google Scholar for
  Related articles
    Email Alert *
    Add to My List *
* Registration required (free)  
 


 
    Abstract
    Introduction
    Clinical Picture
    Genetics
    Renal Manifestations
    Colchicine
    Conclusion
    Acknowledgement
    References
 

 Article Access Statistics
    Viewed5633    
    Printed115    
    Emailed0    
    PDF Downloaded590    
    Comments [Add]    

Recommend this journal