Pulmonary nocardiosis associated with nephrotic syndrome]

A 70-year-old man treated for 6 months with prednisolone for nephrotic syndrome, was referred to our pulmonary division because of a nodule in the right lower lung field. Nocardia asteroides was isolated from the culture of the percutaneous lung aspiration, and the case was diagnosed as pulmonary nocardiosis. The lesion disappeared after 2 months of therapy with sulfamethoxazole/trimethoprim (1,600 mg/320 mg once a day). Though it had been given prophylactically (800 mg/160 mg twice a week) for the prevention of pneumocystis carinii pneumonitis.     

Use of Rituximab in the Antiphospholipid Syndrome

B cells are promising targets for treatment in autoimmune diseases. Rituximab, a chimeric anti-CD20 monoclonal antibody that depletes B cells, is approved for use in rheumatoid arthritis and is often used to treat refractory autoimmune thrombocytopenia. There is increasing interest in using rituximab in other autoimmune diseases, including the antiphospholipid syndrome. We reviewed the published clinical experience of rituximab use in patients with the antiphospholipid syndrome. Data are limited to case reports and small case series. In 19 of 21 reported cases, rituximab appeared to have a beneficial clinical effect. Antiphospholipid antibodies levels were significantly decreased in ten of 12 cases. Controlled clinical trials are needed to determine if rituximab is effective in the antiphospholipid syndrome.     

Pulmonary sarcoidosis and antiphospholipid syndrome

Various autoimmune diseases have been reported to occur in patients with sarcoidosis. However, coexistence of sarcoidosis and antiphospholipid syndrome (APS) is extremely rare. We describe a 59-year-old female patient with pulmonary sarcoidosis who had preceding APS. Her previous medical history consisted of a miscarriage and ischemic colitis. She was diagnosed as APS during the onset of a brainstem infarction with positive reaction to beta2-glycoprotein I-dependent anticardiolipin antibody. Two years later, chest CT revealed enlargement of the hilar and mediastinal lymph nodes and small nodules in the lung fields. Transbronchial lung biopsy demonstrated non-caseating epithelioid cell granuloma leading to the diagnosis of definite pulmonary sarcoidosis. This is the first APS case where pulmonary involvement with sarcoidosis has been confirmed through lung biopsy. Our case report suggests that APS should be recognized as an accompanying disorder of sarcoidosis.     

Results of Aggressive Resection of Lung Metastases from Colorectal Carcinoma Detected by Intensive Follow-Up

PURPOSE: Although outcome of resection for colorectal carcinoma has improved, about 30 percent of patients develop metastatic lesions. Small pulmonary metastases 1 cm or less in diameter now can be detected by diagnostic tests including chest radiography and computed tomography. We evaluated results of our strategy for intensive follow-up after resection of colorectal cancer and aggressive resection of lung metastases disclosed by these periodic examinations. METHODS: Our follow-up program for lung metastasis includes a serum carcinoembryonic antigen assay every two months and chest radiography every six months. Surgical resection of lung metastases was performed if the primary and any nonpulmonary metastases had been controlled, lung metastases numbered four or fewer, and pulmonary functional reserve was adequate. Standard operation for lung metastasis was lobectomy, and lymph node dissection was added in cases of tumor size over 3 cm. Forty-two patients underwent 50 lung resections for metastatic colorectal cancer between 1992 and 1999. Long-term survival was assessed in terms of clinical variables. RESULTS: Overall five-year survival rate after resection of lung metastases from colorectal cancer was 63.7 percent. Variables significantly affecting postthoracotomy survival were primary tumor histology, number of nodules, and disease-free interval up to appearance of the lung metastases, and primary tumor histology was an independent prognostic factor. CONCLUSION: Intensive follow-up for lung metastases after resection of colorectal cancer and aggressive resection improved postoperative survival rate. Patients with well-differentiated adenocarcinoma of primary tumor, a solitary metastatic nodule, and disease-free interval of at least two years after initial surgery are likely to be long-term survivors.     

Sj?gren's syndrome with multiple bullae and pulmonary nodular amyloidosis]

We report a case of Sj?gren's syndrome with pulmonary involvement diagnosed by open lung biopsy. The patient was a 62-year-old woman with antiphospholipid antibody syndrome. Her chest radiograph and CT scan showed multiple bullae diffusely scattered throughout the lung. The open lung biopsy specimens revealed marked inflammatory mononuclear cell infiltration and nodular amyloid deposits in the bronchiolar walls. The mechanism of bulla formation appeared to be the check valve mechanism caused by the narrowing of the airway by the bronchiolitis. The patient was treated with oral corticosteroids, and her symptoms and laboratory findings became stable.     

Pulmonary hypertension, hemolytic anemia, and renal failure. A mitomycin-associated syndrome

After treatment with mitomycin C, a patient developed pulmonary hypertension with interstitial infiltrates, microangiopathic hemolytic anemia, systemic hypertension, and renal failure with the nephrotic syndrome. Open lung biopsy documented intracapillary fibrin thrombi in the pulmonary vasculature. Renal biopsy documented glomerular and arteriolar changes that were most consistent with a thrombotic-thrombocytopenic-like process. Treatment with corticosteroids, fresh-frozen plasma, and total plasma exchange was ineffective. The patient died six months after the onset. When mitomycin-C therapy is given, the clinician should be aware of the pulmonary, renal, and microangiopathic changes that can be associated with such therapy.     

Myelodysplastic syndromes with nephrotic syndrome

It is sometimes reported that the immunological abnormalities in myelodysplastic syndromes (MDS) induce autoimmune disease (i.e., acute systemic vasculitic syndrome, chronic cutaneous vasculitis, polyneuropathy, relapsing polychondritis, and steroid-responsive pulmonary disorders). We investigated the clinical features of patients with MDS accompanied by nephrotic syndrome. We enrolled 125 patients with MDS who were admitted between January 1979 and May 1996 in this study. The renal function was assessed based on the laboratory data and the findings at the physical examination. The diagnoses of nephrotic syndrome and glomerular disease were established when 24-hr urinary excretion was more than 3.5 g and serum total protein was less than 6.0 g/dl, and when the 24-hr protein excretion was more than 1.5 g. Five patients (4%) had glomerular disease, and three (2.4%) had nephrotic syndrome. Of the five patients with glomerular disease, two had refractory anemia (RA), and three had chronic myelomonocytic leukemia (CMMOL). Three of the total 11 patients with CMMOL were diagnosed as having nephrotic syndrome. Among the CMMOL patients, those with nephrotic syndrome showed higher absolute monocyte numbers than did those without nephrotic syndrome (8830 +/- 4677/microl vs. 3061 +/- 2887/microl, P = 0.03). One CMMOL patient was treated with VP-16 and hydroxyurea. As the white blood cell count in this patient decreased, the 24-hr urine protein excretion and the serum tumor necrosis factor alpha level decreased. The relationship between nephrotic syndrome and CMMOL was not clear. High monocyte count and the serum cytokines in MDS patients may play a partial role in the evolution of glomerulonephritis, and CMMOL may be closely related to nephrotic syndrome.     

Sj?gren's syndrome with multiple bullae due to pulmonary nodular amyloidosis]

We reported a case of Sj?gren's syndrome with pulmonary involvement diagnosed by video-assisted thoracoscopic lung biopsy. The patient was a 54-year-old woman with antiphospholipid syndrome. Her chest radiograph and CT scan showed multiple nodules with or within cystic lesions. The thoracoscopic lung biopsy specimens revealed nodular amyloid deposits associated with bronchiolitis. The mechanism of bulla formation appeared to be a check-valve mechanism caused by the narrowing of the airway due to bronchiolitis with mononuclear cell infiltration. She has no symptoms without respiratory failure or functional impairment, therefore we are following her closely without therapy.     

Antiphospholipid syndrome in autoimmune diseases

Classification criteria for antiphospholipid syndrome were first proposed in 1987, revised in 1999 (Sapporo criteria) and up-dated in 2006. The aim of the study was to analyze associations between clinical and laboratory symptoms of antiphospholipid syndrome in the group of patients with autoimmune diseases, based on recently up-dated classification criteria. 336 patients were enrolled into the study, with the majority (n=235) suffering from SLE. Laboratory determinations included: lupus anticoagulant (LA), anticardiolipin (aCL) and anti-beta2-glycoprotein I (abeta2GPI) (both of IgG and IgM class). Clinical and laboratory symptoms of antiphospholipid syndrome were quite common among patients studied. There was a significant association between laboratory and clinical features of antiphospholipid syndrome, according to recently modified classification criteria.     

Autologous hematopoietic stem cell transplantation for refractory antiphospholipid syndrome causing myocardial necrosis

Autologous hematopoietic stem cell transplantation (HSCT) is currently being evaluated as a treatment for autoimmune diseases, including systemic lupus erythematosus (SLE), that are associated with a very severe prognosis. We describe a 27-year-old woman with SLE with a 10-year history of refractory antiphospholipid syndrome (APS). She developed progressive myocardial necrosis despite treatment with corticosteroids, cyclophosphamide (CYC), cyclosporine, and immunopheresis. After conditioning with CYC, fludarabine, and antithymocyte globulin, autologous HSCT using CD34(+) selection was performed. After transplantation, the clinical symptoms caused by APS remitted, and the serum anticardiolipin antibody level decreased. Remission has persisted for 21 months after transplantation. Although a longer follow-up is required for the assessment of efficacy, autologous HSCT may cure patients with refractory APS.     

Coexistence of five autoimmune diseases: diagnostic and therapeutic difficulties

We report the case of coexistence of five autoimmune diseases in a 36-year-old woman, who initially developed psoriasis. Several years later, the patient was diagnosed with a mixed connective tissue disease and primary biliary cirrhosis (PBC). On admission to the Department of Rheumatology and Connective Tissue Diseases, the patient fulfilled classification criteria of an overlap syndrome systemic lupus erythematosus (SLE) with secondary antiphospholipid syndrome/systemic sclerosis (SSc)/Sjogren's syndrome (SS) with coexisting PBC and psoriasis. The SLE symptoms included discoid lupus erythematosus, arthritis, pancytopenia, antinuclear antibodies and anticardiolipin antibodies. Moreover, the patient met the criteria of antiphospholipid syndrome diagnosed based on preterm delivery before week 34, and high values of anticardiolipin antibodies were found at repeated determinations. The SSc symptoms included sclerodactyly, pulmonary fibrosis with pulmonary hypertension and esophageal dysfunction. The SS syndrome involved xerostomia, xerophthalmia, the positive Schirmer's test and presence of anti-SS antibodies. The literature reports overlap syndromes in various combinations; however, the coexistence of five autoimmune diseases is extremely rare.     

Prospective observational study of antiphospholipid antibodies in acute lung injury and acute respiratory distress syndrome: comparison with catastrophic antiphospholipid syndrome

Detection of antiphospholipid (aPL) antibodies in bronchoalveolar lavage fluid (BALF) of patient with acute respiratory distress syndrome (ARDS) suggests involvement of autoimmune mechanisms in the pathogenesis of ARDS. We investigated whether aPL antibodies could be detected in the serum as well as BALF of patients with acute lung injury (ALI) and ARDS. IgG anticardiolipin, IgG anti-beta2-glycoprotein I, IgG antiphosphatidic acid and IgG antiphosphatidylserine antibodies were detected by ELISA in low titers within the normal range in the BALF and serum of nine patients with ALI and 17 patients with ARDS. However, one out of 27 patients investigated had high levels of aPL antibodies in both BALF and serum. This patient suffered from severe ARDS due to sepsis. The high aPL antibody levels in serum possibly triggered by sepsis were associated with high aPL antibody levels in BALF, which can be explained by high capillary-alveolar permeability. Computed tomography scan revealed widespread infarctions in brain, spleen and kidneys, and pulmonary thromboembolism, suggesting the diagnosis of catastrophic antiphospholipid syndrome.     

Antiphospholipid syndrome, antiphospholipid antibodies, and atherosclerosis

The antiphospholipid syndrome is characterized by arterial and venous thrombosis, as well as pregnancy morbidity, in the presence of elevated levels of antiphospholipid antibodies. These autoantibodies have procoagulant activity, as they affect platelets, humoral coagulation factors, and endothelial cells. In addition, they are proatherogenic, as demonstrated by animal models and by the increased prevalence of cardiovascular diseases in patients with systemic lupus erythematosus and antiphospholipid syndrome. Moreover, antiphospholipid antibodies, including anticardiolipin, anti-β2-glycoprotein-1, and anti-oxidized low-density lipoprotein, are associated with atherosclerosis and its consequences in the general population as well. This autoimmune aspect of atherosclerosis in the presence or absence of an autoimmune disease suggests benefit from development of immunomodulating therapies.     

The Eaton-Lambert syndrome and autoimmune disorders

The Eaton-Lambert syndrome is a myasthenic disorder often associated with small cell carcinoma of the lung. We describe a patient with hypothyroidism and pernicious anemia in addition to this syndrome to document its association with diseases having autoimmune concomitants.     

Nephrotic syndrome and juvenile dermatomyositis

Juvenile dermatomyositis (JDM) is a rare autoimmune disease characterized by proximal muscle weakness, skin lesions, gastro intestinal, pulmonary, cardiac and small nerve damage. Renal involvement has been rarely reported in JDM. This is the report of a 7-year-old boy presented with nephrotic syndrome (NS) and subsequent renal failure. Clinical manifestations of JDM appeared gradually. Renal manifestations could be considered as a rare initial presentation of JDM.     

Serum amyloid A: A potential biomarker of lung disorders

Serum amyloid A is an acute-phase protein with multiple immunological functions. Serum amyloid A is involved in lipid metabolism, inflammatory reactions, granuloma formation, and cancerogenesis. Additionally, serum amyloid A is involved in the pathogenesis of different autoimmune lung diseases. The levels of serum amyloid A has been evaluated in biological fluids of patients with different lung diseases, including autoimmune disorders, chronic obstructive pulmonary diseases, obstructive sleep apnea syndrome, sarcoidosis, asthma, lung cancer, and other lung disorders, such as idiopathic pulmonary fibrosis, tuberculosis, radiation pneumonitis, and cystic fibrosis. This review focuses on the cellular and molecular interactions of serum amyloid A in different lung diseases and suggests this acute-phase protein as a prognostic marker.     

Recurrent hepatocellular carcinoma presenting with superior vena cava syndrome

A 45-year-old male received wedge resection for his small hepatocellular carcinoma in April 1989 and extended right lobectomy for tumor recurrence 8 months later. Unfortunately, recurrent hepatic tumor with lung metastases were found 18 months after the second operation. Both the hepatic and pulmonary recurrent tumors were resected and transcatheter arterial embolization was added for the residual hepatic tumors. He remained symptom free for another 18 months. However, mediastinal lymphadenopathy, superior vena cava thrombus with superior vena cava syndrome, cardiac and brain metastases developed subsequently. He died of increased intracranial pressure. It is rare for hepatocellular carcinoma to have mediastinal metastases, superior vena cava thrombus and superior vena cava syndrome.     

Case of small cell lung cancer complicated with diabetes insipidus and Cushing syndrome due to ectopic adrenocorticotropic hormone secretion]

A 54-year-old woman had been given a diagnosis with scleroderma and interstitial pneumonia due to scleroderma when she was 45 years old. Thirst, with resulting polydipsia and polyuria (about 7 liters/day) were present since May, 2004, and bloody sputum appeared in June of 2004. The patient was admitted to our hospital. Chest CT examination showed multiple nodules in the bilateral lower lung field and multiple movable subcutaneous nodules on the abdomen. Small-cell lung cancer (metastases in the pituitary, subcutaneous tissue, and lungs) was diagnosed by transbronchial lung biopsy and subcutaneous nodule biopsy of the abdomen. The final diagnosis was diabetes insipidus and Cushing syndrome. Chemotherapy was done with CDDP and VP-16, which resulted in reduction of the tumor and improvement in endocrinological findings. Nevertheless, chemotherapy could not be continued because of infected bullae. The patient died of deteriorating illness after 91 sickness days. We concluded that this case was Cushing syndrome caused by ectopic adrenocorticotropic hormone-producing small cell lung cancer, and that it presented with diabetes insipidus because of pituitary metastasis. Therefore, when drastic endocrinological changes are found, it is important to examine for cancer, including lung cancer, as soon as possible.     

Squamous cell lung cancer with minimal-change nephrotic syndrome]

We report a case of squamous cell lung cancer with nephrotic syndrome. A 69-year-old man was admitted because of proteinuria and microhematuria. A plain chest X-ray film on admission showed a large mass in the left-lower lung field. The patient was given a diagnosis of minimal-change-nephrotic syndrome and squamous cell lung cancer. We first treated the nephrotic syndrome with glucocorticoid therapy, and then treated the lung cancer with chemo-radiotherapy. This reduced the lung cancer, alleviated the proteinuria, and completely resolved the nephrotic syndrome. Nephrotic syndrome is generally associated with malignant lymphoma and other nonepithelial neoplasms. As the underlying disease, epithelial neoplasms are less common, but lung cancer is one of the most widely reported. Histologically, most cases of cancer-associated nephrotic syndrome exhibit membranous nephropathy; Minimal-change nephrotic syndrome is rare. Deposits of immunocomplex on glomerular basement membrane are considered to play a pathogenic role in membranous nephropathy. However, the pathogenesis of minimal-change nephrotic syndrome is different.     

A case of catastrophic antiphospholipid syndrome presenting with acute respiratory distress syndrome as the initial manifestation

Antiphospholipid syndrome (APS) is a systemic autoimmune disorder characterized by a combination of arterial or venous thrombosis and recurrent fetal loss, accompanied by elevated titers of antiphospholipid antibodies (aPL). Catastrophic antiphospholipid syndrome (CAPS) is a small subset of APS characterized by widespread systemic thrombotic disease with multiorgan failure. We herein describe an autopsy case of CAPS who developed severe respiratory failure due to acute respiratory distress syndrome (ARDS) as the initial manifestation. Patients with APS may exhibit a broad spectrum of pulmonary diseases. ARDS is the common pulmonary complication in CAPS, although it rarely occurs in APS. Some mechanisms of ARDS in CAPS have been postulated but the precise mechanism is still not clearly understood. It is important to understand that APS or CAPS could be a cause of ARDS since ARDS might develop as the initial manifestation of APS or CAPS as seen in our case. Our case is interesting in that severe respiratory failure due to ARDS was the initial presentation of CAPS. This work was performed at Okinawa Prefectural Hokubu Hospital.