Successful use of Tocilizumab in a patient with nephrotic syndrome due to a rapidly progressing AA amyloidosis secondary to latent tuberculosis

AA (secondary) amyloidosis is one of the most severe and uncommon complications of several rheumatic disorders and chronic infections such as tuberculosis (TB). Successful treatment depends on the control of the underlying inflammatory process, what can lead to an improvement or a regression in organ dysfunction. If the disorder persists, it has been reported in some cases of AA amyloidosis secondary to rheumatic diseases, that the use of biologic therapy is so far the only opportunity to reduce the development of AA amyloidosis and to reverse established deposits. We report herein a case of a latent TB infection complicated by a life-threatening AA amyloidosis presented as nephrotic syndrome. After an adequate antituberculostatic treatment, AA amyloidosis remained active and Tocilizumab (TCZ) was started with a dramatic resolution of the proteinuria, stabilization of the amyloid deposits and improvement in general condition.     

Colchicine-sensitive nephrotic syndrome due to AA amyloidosis

A 28-year-old women is presented who was evaluated for a new-onset postpartum nephrotic syndrome with normal renal function. Histological diagnosis was AA amyloidosis but no underlying disease has been diagnosed despite extensive workup. Complete remission was achieved with colchicine. Upon discontinuation of colchicines, the patient’s nephrotic syndrome flared up but completely responded to reinstitution of colchicine therapy. Remission of this patient’s nephrotic syndrome is thus not attributable to resolution of any “idiopathic” primary disease.     

Ankylosing spondylitis-related secondary amyloidosis responded well to etanercept: a report of three patients

Secondary (AA) amyloidosis is one of the most significant complications of ankylosing spondylitis (AS) that frequently leads to proteinuria and renal dysfunction. Anti-tumor necrosis factor alpha (anti-TNF) agents are promising in inducing clinical remission by suppressing systemic inflammation in AA amyloidosis. We report three cases with AS-related AA amyloidosis that responded well to etanercept therapy. Despite treatment with disease modifying anti-rheumatic drugs, all three patients had active AS, marked proteinuria, impaired renal function, and low serum albumin level. During 1-year treatment with etanercept, all patients experienced gradual improvement in all of these parameters.     

糖皮质激素联合硫唑嘌呤治疗复发性淋巴细胞性垂体炎三例报道

报道3例复发性淋巴细胞性垂体炎(LYH)患者均为女性,其中病例2为老年女性.病例1主要累及垂体前叶,并侵犯海绵窦和视交叉,病例2则主要累及下丘脑和漏斗部,病例3则是垂体前叶和垂体柄均受累.病例1手术后4个月第一次复发,给予大剂量甲基泼尼龙治疗(HDMPT)有效,但停药后14个月再次复发;病例2中等剂量强的松治疗停药16个月后复发,而病例3则在HDMPT治疗,糖皮质激素减量的过程中复发.3例患者复发后均以糖皮质激素联合硫唑嘌呤治疗16周,疗效良好,停药后随访3例患者,MRI显示LYH均无复发,而且病例1和3垂体功能正常.

Abstract：

All three cases of recurrent lymphocytic hypophysitis were female, one of them being 70-yearold postmenopausal woman.Adenohypophysis, cavernous sinus, and optic chiasm were involved in case 1,hypothalamus and neurohypophysis were invaded in case 2, and adenohypophysis and hypophyseal stalk were involved in case 3.Relapse occured 4 months after operation in case 1, then high dosage methylprednisolone pulse therapy (HDMPT) brought about a remission lasting for 14 months before second relapse set in.Relapse occurred in case 2 at 16 months after prednisone treatment was discontinued, and case 3 recurred during the period of dose reduction.All three patients were then treated with glucocorticoid plus azathioprine for 16 weeks, and good response was seen in 3 cases.During follow-up, the symptoms were relieved and significant reduction of lesion was revealed by MRI in all thee patients, and the pituitary function was resumed in case1and 3.     

Tocilizumab dramatically ameliorated life-threatening diarrhea due to secondary amyloidosis associated with rheumatoid arthritis

Severe diarrhea improved dramatically with administration of the humanized anti-interleukin-6 receptor antibody tocilizumab (TCZ) in a patient with secondary reactive amyloidosis, which was associated with rheumatoid arthritis (RA). A 53-year-old woman with RA went into hypovolemic shock because of severe watery diarrhea associated with gastrointestinal amyloidosis. The high-dose prednisolone therapy and glucocorticoid pulse therapy did not improve her intractable diarrhea. After TCZ administration, the life-threatening diarrhea lessened in about 6 h, and her vital signs became stable the next day. Perforation of the small intestine, however, occurred 2 days after TCZ administration. Whether TCZ could have been involved in the perforation in such a short time is unknown. Surgery was successful, and the patient recovered. TCZ may work immediately in diarrhea associated with secondary amyloidosis.     

Hepatotoxicity due to azathioprine in a patient with nephrotic syndrome

Hepatotoxicity due to azathioprine (AZA) is uncommon, and evidence favoring AZA hepatotoxicity in humans remains controversial, since most cases previously described have occurred in patients recuperating from renal transplantation who had underlying diseases that may affect the liver, or who were taking other medications with hepatotoxic potential, or in whom complete or incomplete serologic studies to exclude viral hepatitis were absent. We describe a young man with nephrotic syndrome due to minimal change disease, in whom biochemical evidence of hepatocellular damage developed 6 weeks after initiation with AZA therapy. The liver damage completely resolved after drug withdrawal and recurred 4 days after a second challenge with AZA. The present case provides additional evidence that, in humans, AZA could be hepatotoxic.     

Reversal of nephrotic syndrome due to reactive amyloidosis (AA-type) after excision of localized Castleman's disease

The patient (TAL), a chronic asymptomatic HBV carrier with HBsAg-anti-HBsAg circulating immune complexes, was admitted to our hospital because of a nephrotic syndrome due to renal amyloidosis. There was no family history of hereditary amyloidosis. Recurrent arthralgias, asthenia, and weight loss were the prominent clinical features. Laboratory test results showing that severe chronic inflammatory activity had been present for 6 years. Interleukin-6 (IL-6) serum concentration was 10 times normal and C-reactive protein was 1.9 mg/ml. A complex immunological picture was also present (immune complex formation, exuberant B-cell reactivity, and decrease in the number of CD4 T cells). A localized form of Castleman's disease (CD) (plasma-cell type) was diagnosed by surgical excision of a giant axillary lymph node. AA amyloid was present in the blood vessels. Within 60 days after excision of the mass, the systemic symptoms subsided, laboratory signs of inflammatory activity disappeared and IL-6 serum concentration returned to normal, thus establishing a causal relationship between the localized Castleman's disease, elevated IL-6 concentration and the chronic inflammation responsible for AA amyloidosis. At 10 months of follow-up, the nephrotic syndrome has reversed, kidney function has slowly ameliorated, and the patient has gained 12 kg. Abdominal fat aspirates drawn to search for amyloid, positive before surgery, were subsequently negative. The latter finding, and the remission of the nephrotic syndrome, provided strong evidence for regression of the amyloid deposits. However, the HBsAg-anti-HBsAg immune complexes and depression of T-helper cell activity persist. This immunological derangement is therefore not a consequence of CD. Chronic stimulation of the immune system due to the patient's inability to eliminate HBV, in the contest of perturbed immunity, may have favored the genesis of the lymphadenopathy. © 1994 Wiley-Liss, Inc.     

Familial Mediterranean fever with amyloidosis associated with novel exon 2 mutation (S1791) of the MEFV gene

Familial Mediterranean fever (FMF) is an autosomal recessive disorder characterized by recurrent attacks of fever, serositis, and a risk for AA amyloidosis. FMF is caused by mutations in the Mediterranean fever gene (MEFV), which is expressed in blood cells of the myelomonocytic differentiation pathway. We identified a novel mutation S1791 in exon 2 of MEFV in two members of a family of Turkish origin. In both cases, S1791 was in compound heterozygosity with MEFV mutation M694V, and the characteristic clinical syndrome of FMF including amyloidosis was found. The location of S1791 in exon 2 is of interest because (1) amyloidosis in FMF has previously been found to be strongly associated with compound exon 10 mutations and (2) it supports the notion that the mechanism causing FMF is connected to the cytoplasmic rather than nuclear function of the molecule.     

Regression of the nephrotic syndrome in rheumatoid arthritis and amyloidosis treated with azathioprine

Secondary or reactive (AA) amyloidosis is a well-known complication of certain rheumatic diseases, particularly rheumatoid arthritis (RA). This case report describes a patient with RA complicated by amyloidosis and the nephrotic syndrome, which regressed after treatment with azathioprine. The AA amyloidosis was documented by renal and lymph node biopsies and by the presence of proteinuria. Evaluation for other etiologies of proteinuria was negative. After treatment with azathioprine, the proteinuria resolved and the serum albumin level increased from 1.9 mg/dl to normal. This is the first published report of azathioprine therapy resulting in a reversal of the nephrotic syndrome in a patient with RA and secondary amyloidosis.     

Cardiac amyloidosis: A report of two cases

Cardiac amyloidosis is a manifestation of multisystem disorder. The condition is rare, difficult to diagnose and invariably fatal. We report 2 cases of amyloidosis associated with plasma cell dyscrasia. A high index of clinical suspicion, echocardiographic clues (ventricular thickening, diastolic dysfunction, biatrial enlargement) and elevated cardiac biomarkers led to the diagnosis. Early institution of amyloid specific treatment should be the aim. Cardiac treatment is supportive and results are often disappointing.     

An unusual complication of familial Mediterranean fever: protracted arthritis with bilateral coxarthrosis and intraosseous amyloidosis of femoral head

Abstract

Protracted arthritis is uncommon in familial Mediterranean fever (FMF) and rarely may result in degenerative joint damage, a well-known complication of FMF, usually affecting kidneys. We present an unusual case of FMF involving severe bilateral coxarthrosis leading to residual incapacity that was treated by total hip arthroplasty, and an unusual presentation of amyloidosis – intraosseous amyloidosis of the femoral head.     

An unusual complication of familial Mediterranean fever: protracted arthritis with bilateral coxarthrosis and intraosseous amyloidosis of femoral head

Protracted arthritis is uncommon in familial Mediterranean fever (FMF) and rarely may result in degenerative joint damage, a well-known complication of FMF, usually affecting kidneys. We present an unusual case of FMF involving severe bilateral coxarthrosis leading to residual incapacity that was treated by total hip arthroplasty, and an unusual presentation of amyloidosis – intraosseous amyloidosis of the femoral head.     

Successful treatment of an acquired haemorrhagic diathesis due to factor X deficiency with chemotherapy

A 70-yr-old woman presented with a severe haemorrhagic diathesis due to an acquired factor X deficiency. A plasma infusion study showed that exogenous factor X was eliminated very effectively from the patient's circulation. A bone marrow biopsy was consistent with plasma cell dyscrasia. Neither an abdominal fat biopsy nor the bone marrow biopsy confirmed an amyloidosis, although clinically no other diagnosis seemed possible. Treatment with intermittent chemotherapy, consisting of vincristine, cytoxan and prednisone, yielded definite clinical and laboratory improvement.     

Primary systemic amyloidosis presenting as angina pectoris due to intramyocardial coronary artery involvement: a case report

We describe a 76-year-old Japanese woman with primary systemic amyloidosis who presented with angina pectoris associated with ST-segment and T-wave abnormalities resulting from intramyocardial coronary artery amyloidosis. The patient was admitted to our hospital because of dyspnea and pretibial edema 7 years after the diagnosis of variant angina. A diagnosis of primary systemic amyloidosis (AL amyloid protein) was made after examination of gastric and endomyocardial biopsy specimens. The patient died of progressive, uncontrolled heart failure 3 months later. An autopsy study demonstrated only mild-to-moderate atherosclerosis in the epicardial coronary arteries. However, histological examination of the heart revealed diffuse stenoses and obstructions in the intramural coronary arteries by amyloid deposits. This patient had small-vessel coronary disease with ST-segment changes and angina caused by cardiac amyloidosis. A correct diagnosis of ischemic heart disease due to primary amyloidosis is important for estimation of the prognosis and for appropriate management. Received: November 5, 2001 / Accepted: February 5, 2002     

Cardiac amyloidosis presenting as recurrent acute coronary syndrome with unobstructed coronary arteries: Case report

Amyloidosis is a systemic disorder characterized by the deposition of mis-folded protein molecules within various organs. Cardiac involvement may be the presenting feature of this condition or may be identified incidentally during investigation for amyloidosis affecting other organs. The presence and severity of cardiac involvement varies with the type of amyloidosis.Irrespective of the subtype, patients with cardiac amyloidosis usually present with symptoms of heart failure with echocardiography showing features of restrictive cardiomyopathy. The usual cardiac symptoms noted in patients with amyloidosis include dyspnea, peripheral edema, and palpitations secondary to arrhythmias.¹ Chest pain secondary to myocardial ischemia is an unusual presentation of cardiac amyloidosis, and is attributed to the deposition of protein molecules in the coronary microvasculature. We describe the case of a patient who presented with recurrent cardiac ischemia secondary to amyloidosis.     

支气管镜介入联合治疗原发性气管内淀粉样变性12例分析

目的探讨原发性气管内淀粉样变性治疗的有效方法。方法通过收集12例气管内淀粉样变性患者的资料,分析其临床表现、影像学表现、支气管镜下表现、镜下联合介入治疗方法、治疗后反应以及随访结果。结果12例患者经氩气刀、冷冻并术后局部喷洒环磷酰胺的联合介入治疗方法,通过5～17周期的反复治疗及1年的随访,取得了较为满意的临床治疗效果。结论支气管镜下氩气刀、冷冻并局部喷洒环磷酰胺的联合治疗方法可作为气管内淀粉样变性患者的有效治疗选择途径之一在临床开展应用。     

Amyloid goitre in familial Mediterranean fever: report on three patients and review of the literature

Familial Mediterranean fever (FMF) is a hereditary disease, the most threatening complication of which is systemic amyloidosis. The thyroid gland may be asymptomatically involved in most patients with systemic amyloidosis secondary to FMF. However, clinically detectable thyroid goitre is quite rare, and until now only nine cases of thyroid goitre secondary to amyloid deposition in FMF have been reported. Of 1,100 FMF patients regularly followed up at our centre, thyroid goitre due to the accumulation of amyloid substance could be detected in only three (0.27%). In this report, we summarise the clinical and laboratory features of these patients. All three patients were euthyroid. Total thyroidectomy was performed for compressive symptoms in one patient and for aesthetic purposes in the other two. In countries with a high prevalence of FMF, such as Turkey, secondary amyloidosis of the thyroid gland should be borne in mind in long-standing FMF patients.