Cardiac amyloidosis revealing multiple myeloma

INTRODUCTION: Amyloidosis is a rare disease characterized by an extracellular accumulation of a protein polysaccharid complex (Amyloid). Cardiac involvement is considered as a major prognostic factor. OBSERVATIONS: We report the case of two women, hospitalized for heart failure. The diagnosis of cardiac amyloidosis was suggested by echocardiography: Left ventricular concentric hypertrophy and typical amyeloid infiltration with hyperechoic, shiny and granite-like aspect of the interventricular septum. The histological confirmation was obtained by gastric biopsy in the first case and biopsy of the salivary glands in the second revealing an amyloidosis AL. This cardiac amyloidosis was secondary to multiple myeloma: monoclonal Gammopathy with immunoglobulin Lambda in the first and Kappa in the second, and the presence of a plasmocyte infiltration in the sternal puncture. CONCLUSION: Amyloidosis is a rare pathology, the cardiac involvement is frequent in the type AL and can occur with or without clinical manifestations. Echocardiography should be systematic in patients with confirmed amyloidosis.     

AL amyloidosis

AL amyloidosis is a systemic disease characterised by pathogenetic proteins produced by malignant plasma cells and the deposition of them in different organs of the body. Amyloidogenic protein is the light chain of the monoclonal immunoglobulin, which becomes water insoluble, precipitates and deposites in the extracellular space resulting damage of organ function. AL amyloidosis belongs to plasma cell dyscrasias or it can associate to other monoclonal B-cell diseases. Diagnosis - such as in case of other types of amyloidosis - is based on histology. Identification of the amyloidogenic protein often needs special examinations. The goal of the therapy is the eradication of the malignant cell clone. Therapeutical armamentarium has been largely flared in the past few decades, several drugs with new mechanisms of action are available (thalidomide, lenalidomide, bortezomib). The standard treatment is high dose chemotherapy followed by autologous stem cell transplantation in case of eligible patients. Transplantation uneligible patients can be treated with a low dose alkylating agent with or without dexamethasone, or with the new agents. The therapeutical decision must be preceded by very thorough risk assessment. Early diagnosis and the prompt beginning of the treatment has great significance because the evolving functional abnormalities of parenchymal organs (mainly cardiac failure) prevents the effectivity of the treatment. Amyloidosis is an orphan disease, special centers play a significant role in the field of clinical trials.     

Mucocutaneous manifestations of amyloidosis

Amyloidosis is the collective term for a group ofuncommon metabolic disorders in which insoluble amyloid protein-fibres are deposited in tissues and organs. Mucocutaneous manifestations are frequently found in this disease. The different types ofamyloidosis are divided into a systemic and a non-systemic group. Systemic amyloidosis is characterised by amyloid deposits in several organs. In the most frequent type, amyloid light chain (AL) systemic amyloidosis, the skin is involved in 29-40% of the cases. These mucocutaneous manifestations are sometimes the first clue to the discovery of systemic involvement. The non-systemic group comprises primarily localised amyloid deposits in skin and mucosa. The treatment of localised mucocutaneous amyloidosis is aimed at the local changes themselves. The mucocutaneous manifestations due to systemic amyloidosis may improve when it is possible to treat the underlying disease successfully.     

AL-amyloidosis and its treatment by eliminating the precursor protein

AL amyloidosis was diagnosed in 2 patients, women aged 61 and 43 respectively. The first patient, who had a nephrotic syndrome, died soon after diagnosis as the disease appeared to be already widespread. The second patient was still alive at the last follow-up, 17 years after diagnosis, because of effective elimination of her light chains by high-dose chemotherapy. AL amyloidosis is a rare, but severe, systemic disease with high mortality. Its aetiology lies in deregulated plasma cells producing excessive numbers of free immunoglobulin light chains. These light chains are the precursor proteins of amyloid fibrils. Amyloid fibrils are deposited extracellularly in tissue leading to organ dysfunction. Symptomatology is diverse, often non-specific, and generally not very well-known. Therefore, the diagnosis is often delayed for a long time. This is unfortunate, as high-dose chemotherapy targeted at elimination of the precursor protein considerably improves prognosis. However, this type of therapy can only be given in patients with limited and moderately progressive disease.     

Amyloidosis induced colonic stricture. The first symptom of myeloma multiplex. A case report

Systemic amyloidosis often involves the gastrointestinal tract and usually presents as ulceration or polypoid lesions. However, annular stricture of the colon due to amyloidosis is very rare. Amyloidosis develops in appr. 10% of multiple myeloma patients with lambda light chain production, it is usually type AL and not a presenting symptom. CASE REPORT: A 73-year-old female patient appeared at our hospital with anaemia, abdominal pain and haematochesia. Colonoscopy revealed a circular narrowing of the sigmoid colon suggesting malignancy. The patient underwent sigmoid resection and rectosigmoideal anastomosis was prepared to relieve mechanical obstruction. Surprisingly the histological finding from the resected specimen was amyloidosis. Subcutaneous fat tissue biopsy established the diagnosis of systemic AA amyloidosis. Immunoelectrophoresis revealed an elevated gamma-globulin fraction with IgG lambda monoclonal component, as well as a different lambda light chain. Therefore bone marrow biopsy was carried out which confirmed the diagnosis of multiple myeloma. DISCUSSION: Our case is a rare example of the extraordinary tumor-mimicking colon amyloidosis that led to the diagnosis of multiple myeloma. Beside haematological treatment, strict follow-up of the colon process and reconsideration of surgical therapy or endoscopic stenting is of great importance.     

Lymphangioleiomyomatosis. A series of three case reports illustrating the link with high oestrogen states.

Lymphangioleiornyomatosis is a rare lung disorder characterised by cystic air spaces and smooth muscle proliferation. The condition, which most commonly presents with dyspnoea, pneumothoraces or cough, is only described in females and is most commonly diagnosed during childbearing years. Three cases are presented which illustrate typical features of the disease and the association with high oestrogen levels. The first had recurrent pneumothoraces during her first pregnancy. The second lady was post menopausal at diagnosis but her symptoms predated her menopause. The third, presented with dyspnoea, abnormal chest sensations and a pneumothorax. She had a history of hyperprolactinaemia with secondary amenorhoea due to low oestrogen levels which had been corrected prior to her presentation. All three patients had reduced gas transfer and abnormalities in spirometry, two had reticular shadowing on their chest radiograph and all had typical appearances on lung computerised tomography. Although disease progression was variable, all patients showed a gradual decline in lung function.     

Amyloidosis and the digestive tract

Amyloidosis is one of the unusual diseases which may still be underdiagnosed when it is affecting the patient. During the last three decades, an enormous progress has been made in understanding and improvement of the biochemical nature, classification, pathogenesis, clinical features, diagnostic measures and rational therapy of this disorder. The varied clinical presentation of gastrointestinal amyloidosis makes the diagnosis challenging. It should be considered in patients older than 30 years with otherwise unexplained diarrhoea, weight loss, motility dysfunction or malabsorption.     

Lung function and chest radiograph abnormalities among construction insulators.

We carried out a prevalence survey of pulmonary health parameters among current and retired construction insulators (50 years old and older) from all areas of British Columbia, Canada. The study population included 59 active workers (81 percent participation in this group) and 29 workers who were retired or inactive due to illness (69% participation). Radiograph results were compared to those from actively working bus mechanics from the same age group, and retired grain and civic workers, who were all tested in the same manner. Chest radiographs were read independently by two readers and were graded according to the ILO classification system. Pleural abnormalities alone were found in 34% (20) of active workers (5% in comparison group) and 45% (13) of non-active workers (14% in comparison group). Rates for parenchymal abnormalities for these same groups (ILO grade 1/0 or higher) were 17% (5%) and 20% (5%), respectively. Airflow obstruction was present in 35% (31) of the insulators and was associated with age and the presence of diffuse pleural thickening, and 5 or more years of employment in pulp mills. Restrictive lung function was present in 22% (19) of the insulator population and was associated with age and radiographic evidence of parenchymal fibrosis. The results indicate that construction insulators, a group at high risk for asbestos-related lung disease, also have a high prevalence of airflow obstruction. This was associated not only with smoking, but also with diffuse pleural thickening and a history of pulp-mill employment, suggesting that airflow obstruction in this population is also partly work related.     

Interstitial lung disease in mixed connective tissue disease

INTRODUCTION: The authors analyzed the incidence of interstitial lung disease in mixed connective tissue disease. They were seeking an answer to the following problems: the nature of the pathological course of mixed connective tissue disease complicated by and the therapy to be used in interstitial lung disease. PATIENTS AND METHODS: 179 patients were followed up during a period of 15.9 +/- 6.1 years. Interstitial lung disease was diagnosed using high resolution computed tomography. The diagnosis of interstitial lung disease was not obvious in 5 patients thus open lung biopsy was performed, which confirmed common interstitial pneumonitis. The patients were followed-up, and the data of computed tomography and respiratory function tests were detected 6 months, and then 4 years after the acute lung disease complicated by mixed connective tissue disease. RESULTS: Out of the 179 mixed connective tissue disease patients 96 (53.6%) had interstitial lung disease. The onset of interstitial lung disease was the most frequent in the 2-4 years of the disease. Four years after the first appearance of interstitial lung disease severe fibrosis was diagnosed in 24 patients (25%). A honey comb formation in the lung developed only in one patient. For the treatment of interstitial lung disease, corticosteroid treatment had to be combined with cyclophosphamide in 51 cases. In 4 patients (24%), pulmonary arterial hypertension evolved 2-4 years following interstitial lung disease. The high pulmonary arterial pressure decreased using pulsed corticosteroid treatment, cyclophosphamide, prostacyclin analogue, anticoagulants therapy and the 4 patients stay alive. The pulmonary arterial hypertension was caused by obliterative vasculopathy. CONCLUSION: Pulmonary involvement is found in more than half of the patients with mixed connective tissue disease. Early diagnosis of interstitial lung disease is possible by computed tomography. Interstitial lung disease can be treated by the combination of corticosteroids and cyclophosphamide. The authors were the first to detect the coexistence of interstitial lung disease and pulmonary arterial hypertension in mixed connective tissue disease. Subsequent respiratory alterations in these patient necessitate regular patient follow up.     

Lithium, a potentially dangerous drug

Two patients with a bipolar disorder, a woman aged 56 and a woman aged 68, who had used lithium for more than 30 years, were seen with side effects from this medication. Both patients were treated by their general practitioner and had not visited a psychiatrist for many years. The first patient had a chronic lithium intoxication with cerebellar signs and eventually coma, diabetes insipidus, hyperthyroidism, hyperparathyroidism and psoriasis. After 6 weeks of treatment in the intensive-care unit she made a good recovery. The second patient had several lithium side effects. She was diagnosed with diabetes insipidus, hyperparathyroidism due to a parathyroid adenoma, hypothyroidism and a sick-sinus syndrome. A pacemaker was implanted 4 years earlier. The adenoma was surgically removed. After other medication was tried, the patient was once again given lithium, on which she was able to function well. The first patient had lithium concentrations above the therapeutic value for several years and both patients experienced a delay before their signs and symptoms were attributed to lithium. Lithium treatment should be monitored by an experienced psychiatrist.     

Pulmonary damage after radiotherapy for breast cancer]

Radiation therapy for breast cancer can cause pulmonary damage. This was diagnosed in two patients aged 75 and 57 years respectively. They had different types of radiation pneumonitis. The first patient presented with a so-called bronchiolitis obliterans organizing pneumonia (BOOP), four months after radiation therapy. Characteristic in BOOP are the bilateral and migrating lung infiltrates that are distributed predominantly in the middle and lower lung zones. The second patient developed a pneumonitis that classically was confined to the area of irradiation four months after radiation therapy. The two types of radiation pneumonitis can be treated successfully with corticosteroids. If symptomatic radiation pneumonitis is diagnosed early it can be treated well and than has a good prognosis.     

Two neonates with congenital aniridia: the necessity of genetic investigation

Two female neonates were diagnosed post partum with bilateral aniridia. The first patient had the familial form, caused by a point mutation in the paired box 6 (PAX6) gene. The second patient had a sporadic aniridia caused by a de novo microdeletion involving both the PAX6 gene as well as the Wilms tumour suppressor-I (WT1) gene. This made screening for the presence of a Wilms tumour necessary. The second patient died several months after birth, due to respiratory insufficiency. Aniridia is a rare developmental disorder of the eye, with absence of most of the iris tissue, caused by an abnormality in the PAX6 gene on chromosome 11p13. Familial aniridia is usually due to a point mutation of the PAX6 gene, which causes solely ocular abnormalities. Sporadic aniridia is caused by a de novo deletion or microdeletion of chromosome 11p13, which affects not only the PAX6 gene but also the adjacent WT1 gene. In these patients, the Wilms tumour, aniridia, genitourinary anomalies, and mental retardation (WAGR) syndrome can be present, and screening for a Wilms tumour is indicated. Unless previous investigation of a family member has demonstrated the WT1 gene to be normal, chromosome studies should always be performed in patients with aniridia.     

Transient cardiac failure due to infectious myocarditis

Two men aged 19 (patient A) and 37 (patient B) years respectively, presented with symptoms of general malaise, fever and nonspecific ECG abnormalities. After admission both patients developed shock. Cardiac ultrasound revealed severe left ventricle dysfunction. On the basis of these findings, infectious myocarditis was suspected. Patient B was placed on artificial ventilation and haemodialysis due to respiratory and renal failure. Both patients were treated with inotropic drugs and antibiotics. Neisseria meningitidis was established as the cause of the myocarditis in patient A but in patient B no cause was found despite microbiological and autoimmune investigations. PCR tests and a biopsy of the myocardium were not performed. There was a satisfactory recovery in the left ventricle function of both patients during admission. These two cases illustrate that (infectious) myocarditis should be suspected in patients presenting with symptoms of general malaise, fever and nonspecific ECG abnormalities. If (infectious) myocarditis is diagnosed, the patient should be monitored for severe heart failure.     

CT findings of the benign tracheobronchial lesions with calcification

In the benign tracheobronchial lesions with calcification, tracheobronchopathia osteochondroplastica, relapsing polychondritis and tracheobronchial amyloidosis were considered. CT demonstrated small nodules with calcifications at the trachea with or without deformity of tracheal wall in the case of tracheobronchopathia osteochondroplastica, swelling of tracheal cartilage with diffuse and multiple calcifications in the case of relapsing polychondritis and calcifications in the deep parts of tracheobronchial amyloid nodules. CT findings were able to differentiate those benign lesions. High-resolution CT is more useful in the distribution of abnormal calcification of these diseases.     

Lymphoma in patients who have undergone organ transplantation: severe and variable clinical presentation

Two patients presented with post-transplant lymphoproliferative disorder (PTLD). PTLD encompasses a broad range ofoften malignant proliferations of lymphoid tissue arising in the immunocompromised host after transplantation. The first patient, a 62-year-old woman, received a bilateral lung transplant due to end-stage emphysema and was diagnosed with PTLD 27 days after transplantation. Treatment consisted of reduction in immunosuppression and administration of rituximab. The PTLD regressed. The second patient, a 57-year-old woman, presented with a massively disseminated PTLD 12 years after kidney transplantation. Immunosuppression was reduced and rituximab was administered, but no response was observed. Despite salvage chemotherapy, the patient died due to progressive disease. These two cases illustrate the heterogeneous presentation of PTLD. The condition is caused by the proliferation of B lymphocytes infected with Epstein-Barr virus (EBV) that are no longer controlled by EBV-specific cytotoxic T lymphocytes, due to the immunosuppressive medication given to prevent transplant rejection. Regression of the lymphoma may be achieved by reducing the immunosuppression or treating with rituximab, which attacks B lymphocytes.     

经支气管镜肺活检30例肺部弥漫性疾病全程护理体会

目的探讨经支气管镜肺活检（TBLB）肺部弥漫性疾病的操作及全程护理体会。方法对30例肺部弥漫性疾病行TBLB检查患者实施全程护理,并对临床资料、病理诊断结果、并发症及护理体会进行回顾分析。结果 30例弥漫性肺疾病均成功取得肺组织标本,20例明确诊断,确诊率达66.7%。患者耐受性良好,术后发生气胸4例（13.3%）、咯血5例（16.7%）。结论在支气管镜肺活检过程中实施全程护理有助于提高手术成功率。     

Pulmonary function,smoking habits,and high resolution computed tomography (HRCT) early abnormalities of lung and pleural fibrosis in shipyard workers exposed to asbestos

To evaluate the presence of asbestos-related pleural and parenchymal abnormalities and their correlation with pulmonary function and smoking habits, 119 asbestos-exposed asymptomatic workers (mean age, 46.2 years; mean duration of asbestos exposure, 8.6 years; mean latency time, 21.6 years) with normal standard P-A chest radiographs were submitted to HRCT, CO-diffusing capacity, and pulmonary function tests. HRCT scans were normal only in 31 (26%) examined workers; 31 (26%) subjects showed both pleural and parenchymal involvement, and 50 (42%) and seven (6%) had exclusively pleural and parenchymal abnormalities, respectively. Based on CO-diffusing capacity and pulmonary function tests, no significant difference was demonstrated between workers with pleural lesions and subjects with normal pleura; however, lower values of FVC were observed in the nonsmoking workers with parenchymal abnormalities in comparison with nonsmoking subjects with normal parenchyma (78.2 vs. 89.7% of predicted values; p = 0.03 by student's two-tailedttest), and lower values of FEV₁/FVC in the smokers with parenchymal lesions with respect to smokers with normal parenchyma (93.7 vs. 100.2% of predicted values; p = 0.005 by student's two-tailedttest). In conclusion, our results demonstrate that HRCT may detect early parenchymal abnormalities which correlate with exposure to asbestos and respiratory function impairment, including a reduction in obstructive indices in smokers occupationally exposed to asbestos, without any clinically evident disease. © 1996 Wiley-Liss, Inc.     

Pulmonary function in long-term asbestos workers in China

The relationship of pulmonary function to exposure to asbestos and radiographic abnormalities has been controversial, especially when smoking is present as a confounder. The aim of the study was to provide further understanding on the radiographic-physiologic associations in nonsmoking and smoking asbestos workers. Radiographic asbestosis, pleural lesion, and pulmonary function were studied in 269 Chinese asbestos workers, with average exposure years of 23 for male workers and 18 for female workers. Their functional data were compared with those of 274 controls without exposure to dust. Although most of the male workers were smokers, none of the female workers smoked. In comparison with controls, asbestos workers had significantly lower lung volume and diffusing capacity, irrespective of gender. Female workers and smoking male workers had lower measurements of forced expiratory volume in 1 second and instantaneous forced expiratory flow at 50% and 25% of forced vital capacity. After adjustment for relevant covariates, asbestos exposure, asbestosis, and pleural abnormalities were associated with decreased parameters of pulmonary function, including lung volume, diffusing capacity, and airway flow. These data indicate that asbestos-related functional defects manifested by lung restriction and mild airway obstruction correlate with exposure to asbestos and with parenchymal and pleural abnormalities, independent of smoking.     

Mechanical ventilation in neuromuscular diseases: do not start too early, but certainly not too late

Three patients had chronic respiratory disorders: a 42-year-old man with glycogenosis type II was tired, had headaches, poor pulmonary function values and, according to the arterial blood gas values, hypercapnia; a man aged 24 with Duchenne's muscular dystrophy had variable moderate dyspnoea with hypoxia and hypercapnia, and a man aged 64 years with an mitochondrial myopathy complained of dyspnoea and headache but had good blood gas values. The symptoms and abnormalities of the first patient were suppressed by nocturnal ventilatory support through a nasal mask system, the second preferred to refrain from ventilatory support and died a few weeks later and the symptoms of the third patient decreased without ventilatory support. Assessing a ventilatory disorder in patients with a neuromuscular disease is not always simple. Symptoms suggestive of nocturnal hypoventilation may occur in patients without respiratory insufficiency. It is also possible for patients with chronic respiratory insufficiency to be free of symptoms. Determinations of the arterial blood gas values are the most reliable method. Since normal daytime values do not exclude a nocturnal respiratory insufficiency, it is advisable in case of suspicion of nocturnal hypoventilation to measure the arterial blood gas values at night, as well. Nocturnal pulse oximetry does not always adequately reflect the degree of hypoventilation. In view of the positive effects of assisted respiration, adequate diagnostic examinations and early referral to a centre for home mechanical ventilation are advisable.     

Characterisation of respiratory health and exposures at a sintered permanent magnet manufacturer.

Sintered permanent magnets are made from the powdered metals of cobalt, nickel, aluminium, and various rare earths. During production, exposure to respirable crystalline silica and asbestos may also occur. Reported here is a cross sectional study of 310 current and 52 retired hourly employees who worked 10 or more years making sintered magnets. Each participant had a chest radiograph, spirometry, and completed a respiratory questionnaire. Illness logs were also reviewed to calculate the incidence of recorded respiratory disorders. The prevalences of abnormalities in pulmonary function and respiratory symptoms were not higher than found in an external referent population. Although the prevalence of diffuse parenchymal opacities consistent with pneumoconiosis (four workers) was similar to the referent population, one worker had radiographic findings consistent with silicosis and two workers had profusion scores of 1/2 or above, not seen in the referent group. The incidence of reported respiratory conditions in the log, including asthma, was 10 times that of other manufacturers in the same industrial classification category. Excessive exposures to cobalt, nickel, and respirable silica were shown by environmental measurements.