Low serum apolipoprotein AI levels in amyloidosis related to familial Mediterranean fever

Amyloidosis (A) related to familial Mediterranean fever (FMF) causes serious morbidity and mortality in children. Our study evaluates serum levels of apolipoprotein (Apo) AI, AII, B, and E and Apo AII/AI ratios as a non-invasive diagnostic tool for amyloidosis in children with FMF and FMF-A. Results were compared with those of patients with childhood nephrotic syndrome (NS) and healthy children (controls). Significantly lower serum levels of Apo AI (90.20±28.30 mg/dl) were documented in patients with FMF-A than in all other groups (FMF 126.89±51.07 mg/dl, NS 140.38±33.73 mg/dl, and controls 134.67±12.73 mg/dl) (P<0.01). Diagnostic sensitivity, specificity, and predictive value for this test were 85%, 80%, and 85%, respectively. Apo AII/AI ratio results were essentially equal in all groups (P>0.05). It is concluded that a decreased Apo AI serum level, but not Apo AII/AI ratio, is a useful, non-invasive test for the early diagnosis of FMF-A in children.     

Renal, gastric and thyroidal amyloidosis due to familial Mediterranean fever

Chronic renal failure developed in a 10-year-old girl due to renal amyloidosis secondary to familial Mediterranean fever (FMF). During management of the chronic renal failure by hemodialysis and of FMF with colchicine, goiter and hypothroidism were observed. Thyroid fine-needle aspiration and gastric endoscopical biopsies, performed when recurrent abdominal pain could not be controlled, revealed amyloid deposits in both thyroid and gastric tissues. After 6 months’ therapy with colchicine and levothyroxine, there was no significant change in the thyroid volume. This is the first case in which gastric amyloidosis secondary to FMF in childhood has been demonstrated. Patients with amyloidosis secondary to FMF who have thyroid enlargement and unexplained gastrointestinal symptoms despite adequate therapy should be evaluated with imaging studies and biopsy examinations. Received March 29, 1996; received in revised form August 20, 1996; accepted September 12, 1996     

Myositis in a patient with familial Mediterranean fever and spondyloarthritis successfully treated with anakinra

Familial Mediterranean fever is an autosomal-recessive autoinflammatory disorder more commonly observed in Mediterranean populations and characterized by recurrent episodes of fever, serositis, myalgia and arthritis. There is rarely any association with spondyloarthritis. The most important long-term complication is progressive systemic type AA amyloidosis. Treatment with colchicine is effective in reducing the frequency of attacks and prevents the development of amyloidosis. However, 5% of cases are considered resistant to colchicine. We here describe the case of a 39-year-old man, with a history of arthritis, arthralgias, and sacroiliitis in the course of a familial Mediterranean fever. He is homozygous for the M694I mutation in the MEFV gene. He subsequently developed myositis of the right quadriceps muscle confirmed by magnetic resonance imaging, electromyography and histology. He had frequent and severe arthralgias, despite colchicine, then etanercept and adalimumab, impairing his quality of life. The patient was successfully treated with the IL-1 receptor antagonist anakinra with a dramatic improvement of muscular and articular symptoms. To our knowledge, our patient is the first patient with coexisting FMF, spondyloarthritis and myositis responding to anakinra treatment. Moreover this is the second case in the literature of myositis associated with familial Mediterranean fever.     

一个中国汉族家族性IgA肾病家系致病基因的排除性定位

目的 对一个中国汉族家族性IgA肾病（FIgAN）家系进行遗传连锁分析,并对目前国内外已知的5个致病位点进行排除性定位,从而初步定位该家系致病基因的染色体位点。 方法 判断FIgAN的遗传方式。采集家系成员外周血提取基因组DNA。在已报道的FIgAN致病区域（2q36、3p23-24、4q26-31、6q22-23、17q12-22）选取微卫星遗传标记（STR）,进行基因组扫描,应用两点间连锁分析方法对基因分型数据进行分析。结果 该FIgAN家系的遗传方式为常染色体显性遗传。对该家系5个已知致病区域内计26个STR的两点间连锁分析结果显示,最大优势对数（LOD）值为0.39（D17S1868）,不支持与上述5个染色体区域的连锁关系。 结论 该家系致病基因所在染色体区域非目前已报道的5个FIgAN致病位点,提示FIgAN存在新的致病区域,并进一步证明了该病的遗传异质性。     

Variable expression of vasculitis in siblings with familial Mediterranean fever

Familial Mediterranean fever (FMF) is an autosomal recessive disorder characterized by recurrent and self-limited attacks of serosal inflammation with abdominal pain, chest pain, and arthritis usually accompanied by fever. Different vasculitides such as polyarteritis nodosa (PAN) and Henoch-Schönlein syndrome (HSS) may be associated with FMF. We report two sisters of a Turkish family with FMF who developed distinct vasculitides. The younger sister developed severe PAN with perirenal hematoma at the age of 13 years, the older sister presented with severe HSS and acute renal failure at the age of 19 years. Neither sister developed amyloidosis until the age of 30 years. This observation suggests that early events in the pathogenesis of PAN and HSS are generally quite similar.     

The coexistence of familial Mediterranean fever and polyarteritis nodosa; report of a case

We describe a 14-year-old boy with a 5-year history of familial Mediterranean fever (FMF), treated with colchicine, who developed polyarteritis nodosa (PAN). He was admitted to our hospital with fever, general weakness, arthritis, and purpura. Five weeks after admission, hypertension was noted. Skin biopsy showed perivascular leukocyte infiltration in the epidermis. An aortography revealed multiple aneurysms of the renal, common hepatic, and intercostal arteries. He was treated with intravenous methylprednisolone, oral cyclophosphamide, and azathioprine. The known rare association of FMF and PAN is discussed. Received June 14, 1995; received in revised form January 26, 1996; accepted February 9, 1996     

Polyarteritis nodosa in a case of familial Mediterranean fever

We describe a 7-year-old boy with familial Mediterranean fever (FMF) complicated by polyarteritis nodosa (PAN) with distinct angiographic findings. On admission, he had abdominal pain, arthralgia, and severe fibromyalgia. During hospitalization, he displayed maculopapular eruptions, high blood pressure, gastrointestinal bleeding, and persistent constitutional symptoms mimicking a vasculitic process, most probably PAN. Renal angiography showed a perfusion defect compatible with a renal infarction secondary to a vasculitic process. He responded well to pulse methylprednisolone therapy with colchicine. We emphasize the rare association of FMF and PAN and the non-aneurysmal angiographic signs of PAN.     

IgA nephropathy in patients with familial Mediterranean fever

Two patients with a long-standing history of familial Mediterranean fever were found to have both microscopic hematuria and proteinuria during the acute attacks. Kidney biopsies from both patients revealed diffuse mesangial proliferative glomerulonephritis with intense mesangial IgA and C3 deposits and no evidence of amyloidosis. To our knowledge these are the first 2 cases documenting the presence of mesangial IgA nephropathy in patients with familial Mediterranean fever.     

Higher thrombin activatable fibrinolysis inhibitor levels are associated with inflammation in attack-free familial Mediterranean fever patients

Background: Coagulation abnormalities have been reported in familial Mediterranean fever (FMF) patients with amyloidosis and nephrotic syndrome; but there is not enough data about the continuity of the thrombogenic activity in FMF patients in clinical remission. The purpose of this study was to assess thrombin activatable fibrinolysis inhibitor (TAFI) levels and its relationship with fibrinolytic activity and also evaluate relationships between mutations and clinical signs in attack-free patients without amyloidosis. Methods: Seventy-nine FMF patients and 40 healthy adults were included. The study group was divided into five groups as follows: first group, homozygote M694V; second group, homozygote M680I; third group, M694V in one allele, the other allele have other mutations or not; fourth group, other mutations; and fifth group, no mutation. Results: Serum TAFI levels were significantly increased in patients compared with healthy individuals (116.64?±?21.8 vs. 78.48?±?19.7?μg/mL, p?r?=?0.247, p?=?0.029 and r?=?0.252, p?=?0.032, respectively). Mean fibrinogen and TAFI levels were significantly higher in Group 1 than the other groups (p?=?0.04 and p?=?0.001, respectively) and in Group 3 it was higher than Groups 2, 4 and 5 (p?=?0.04 and p?=?0.001, respectively). Conclusions: High level of TAFI antigen in attack-free period of FMF disease shows ongoing subclinical inflammation and hypercoagulability. Clinicians should be careful about thrombosis even in patients at clinical remission. Also, genetic tests must be considered to predict clinical outcome and to reduce complications of FMF disease.     

Familial Mediterranean fever

Familial Mediterranean fever (FMF) is the most frequent periodic syndrome characterized by recurrent attacks of polyserositis. Fever, abdominal pain, chest pain, and arthritis/arthralgia are the leading symptoms. It is an autosomal recessive disorder, which primarily affects Jewish, Armenian, Turkish, and Arab populations. The FMF gene (MEFV) has recently been cloned to chromosome 16p, which encodes pyrin. Genotype-phenotype correlation is not well established. Amyloidosis is the most severe complication of FMF. The SAA1-/ genotype was associated with an increased risk of amyloidosis. Colchicine treatment not only decreases the frequency and severity of attacks, but also prevents amyloidosis. Certain vasculitides, namely Henoch-Schonlein purpura and polyarteritis nodosa, are more frequent among FMF patients.     

Pain relief with oral cannabinoids in familial Mediterranean fever

Cannabinoids have analgesic and, possibly, anti-inflammatory properties but their clinical use has been restricted by legislation. This is the first United Kingdom report of the controlled use of a standardised pharmaceutical preparation of cannabinoids in capsular form. The therapy was assessed in a patient with familial Mediterranean fever, who presented with chronic relapsing pain and inflammation of gastrointestinal origin. After determining a suitable analgesic dosage, a double-blind placebo-controlled cross-over trial was conducted using 50 mg tetrahydrocannabinol daily in five doses in the active weeks and measuring effects on parameters of inflammation and pain. Although no anti-inflammatory effects of tetrahydrocannabinol were detected during the trial, a highly significant reduction (p < 0.001) in additional analgesic requirements was achieved. Future study designs can now incorporate prescribable forms of cannabinoids but the choice of previous cannabis users only as patients has clinical limitations. Cannabis naive patients would tolerate controlled investigations but may generate medicolegal problems.     

Specific binding of circulating IgA antibodies in patients with IgA nephropathy

Detection of circulating IgA antibodies which are specific in patients with IgA nephropathy is described. Freeze and thawed extracts of pharyngeal cells obtained from patients with IgA nephropathy, other glomerular diseases, and healthy adults were cultured with fibroblasts such as Vero or Hel cells at 37 degrees C for 2 weeks. Serum samples were obtained from these patients and healthy adults. The cultured fibroblasts were fixed on slide glasses, and then incubated with the serum samples from the same or other patients with IgA nephropathy. The cells were stained with FITC-labeled heavy-chain specific anti-human IgA antiserum and then examined with a fluorescent microscope. It was demonstrated that the IgA antibodies in sera obtained from patients with IgA nephropathy or HSP nephritis were bound with the nuclear regions of such fibroblasts. It was suggested that IgA antibodies in sera could be bound with some antigenic substances which were transferred from pharyngeal cells of patients with IgA nephropathy to fibroblasts in vitro.     

Massive renal and adrenal calcifications in a young dialysis patient with familial Mediterranean fever

A 34-year-old patient was hospitalized for progressive developmentof asthenia, muscle weakness and weight loss. This Greek manhad familial Mediterranean     

Polyarteritis nodosa type vasculitis in a patient with familial Mediterranean fever treated with cyclosporin A

Patients with amyloidosis secondary to familial Mediterranean fever (FMF) are known to tolerate cyclosporin A poorly. We report a case of severe cyclosporin toxicity in a patient with FMF amyloidosis who underwent kidney transplantation. The clinical syndrome consisted of severe gastrointestinal, neuromuscular, and psychiatric disturbances. Histological examination of the transplanted kidney revealed vasculitis of the polyarteritis nodosa type. We hypothesize that FMF patients are more vulnerable to the acute vascular toxicity of cyclosporin due to defective inhibition of complement activation, leading to a widespread vasculitis of the polyarteritis nodosa type.     

Pathogenesis of idiopathic IgA nephropathy

Despite a prodigious amount of work on the physiology of IgA production in man, and many studies on the immunopathology of IgA nephropathy, ranging from the immunogenetics to the immune response to chemical characteristics of the IgA, we are hardly any nearer to defining the pathogenesis of this disease. One of the main changes in our understanding has been to recognise that the bone marrow, now known to produce normally one-third of the body's IgA, overproduces this immunoglobulin in IgA nephropathy. This alters the previous notion that IgA nephropathy was due simply to IgA production in the mucosa, although a mucosal component is not excluded. Certain characteristics of the IgA in the diseased kidney and the circulation have been defined: it is of subclass IgA1 and has a higher proportion of light chains and negative charge than in normal subjects. The specificities of the IgA, either in the kidney or in complexes, have not helped to clarify the pathogenesis. They have been found for a wide range of endogenous and exogenous antigens, suggesting that the antibody activity represents polyclonal B cell activation. These findings have not helped to confirm the prevailing theory that IgA nephropathy is an immune complex disease. Other theories put forward are that IgA nephropathy is an autoimmune disease, glomerular components or IgA itself being among the candidate antigens, or that there is primary dysregulation of the IgA immune system. At this stage of development in our understanding of this common nephropathy, it is important to guard against the assumption that idiopathic IgA nephropathy is one disease and is the result of a single pathogenetic mechanism.