Thymoma associated with systemic lupus erythematosus and immunologic abnormalities

The association between Systemic Lupus Erythematosus (SLE) and thymoma occurs with a greater frequency than dictated by coincidence alone. The immunologic effects of thymectomy on the appearance and/or the course of SLE are still to be elucidated. We report one case of SLE diagnosed at the same time as thymoma, and two cases of thymoma associated with immunologic disorders in the absence of clinical signs and symptoms diagnostic of SLE.     

Systemic lupus erythematosus and invasive thymoma: report of two cases.

Two cases of invasive thymoma in patients with systemic lupus erythematosus (SLE) are described. In both instances the suspected diagnosis of a mediastinal tumour proved difficult to confirm. Neither surgical removal of the thymoma in one case nor irradiation in the other had any apparent clinical or serological effect on the course of the SLE. Both patients subsequently suffered from respiratory problems and the distinction between recurrent tumour and pulmonary involvement by SLE proved difficult. One patient had a good response, however, to pulse methylprednisolone, but the other later developed recurrence of tumour and died of Pneumocystis carinii infection following cytotoxic therapy three years after discovery of the tumour.     

Lambert-Eaton myasthenic syndrome and follicular thymic hyperplasia in systemic lupus erythematosus

Fatigue is a prominent feature of systemic lupus erythematosus (SLE), usually ascribed to various factors, such as muscle or joint involvement, anaemia or depression. The Lambert-Eaton myasthenic syndrome (LEMS) is a rare autoantibody-mediated disorder of neuro-muscular transmission. We report on a well-defined LEMS associated with thymus hyperplasia in a SLE patient. An African 41 years-old SLE patient presented with persisting fatigue, myalgia and dyspnea, abolished reflexes and a bilateral ptosis. Neuromuscular electrodiagnostic study showed a clear-cut potentiation that was typical of a pre-synaptic neuromuscular junction disease. Anti-calcium gated channels antibodies were disclosed in serum and a diagnosis of LEMS was made. A total body CT-scan revealed an antero-superior mediastinal mass, compatible with thymoma. The tumour was surgically removed with a final diagnosis of follicular thymic hyperplasia. In conclusion, our observation provides a new example of entangled organ-specific and systemic autoimmunity in the context of thymus pathology. Potentiation study during electromyography should be performed systematically to rule out LEMS in patients with SLE and muscle weakness.     

1975-2008年国内外系统性红斑狼疮合并胸腺瘤的临床荟萃分析

切除胸腺瘤后SLE转归多样,27.8%缓解,33.3%恶化,38.9%无变化.结论 对年龄较大的SLE患者应警惕存在胸腺瘤的可能,以糖皮质激素为基础的免疫抑制治疗仍可用于合并胸腺瘤的SLE.不应将切除胸腺瘤作为治疗SLE的方法之一.     

Lupus erythematosus (LE) cells in ascites: initial diagnosis of systemic lupus erythematosus by cytological examination: a case report

Systemic lupus erythematosus (SLE) is an autoimmune disease, involving multiple organs. Diverse manifestations may obscure the diagnosis and confuse our thinking process, especially when few clues are present at the beginning. Serositis is one of the various presentations, and the presence of lupus erythematosus (LE) cell in body fluid may be a hint for the final diagnosis of SLE. Herein, we present a young female patient diagnosed of SLE with initial presentation of lupus peritonitis. Finding of LE cell in ascites prompted us for immunologic survey. Diagnosis of SLE was confirmed with high titer of anti-nuclear antibody and antibody to double-stranded DNA. Cytologic examination of body fluid is mainly useful in detecting malignant cells, but high specificity of this marker aids in early diagnosis of SLE.     

Body composition in systemic lupus erythematosus

The objectives were to determine the body composition, and the effects of disease and corticosteroid therapy on body composition, in a population of female patients with systemic lupus erythematosus (SLE). All female SLE patients managed through a single centre were invited to participate in a cross-sectional study of body composition. Data were collected by standardized interview and examination, and review of medical records. Body composition was assessed by dual-energy X-ray absorptiometry (DXA). Eighty-two subjects were evaluated, 30 of whom were post-menopausal. Univariate linear regression analysis revealed a significant association of reduced fat-free mass with SLE severity [as measured by the Systemic Lupus International Collaborative Clinics (SLICC)] (P = 0.020), a history of corticosteroid exposure (P = 0.043) and age (P = 0.048). Reduced total body bone mineral density (BMD) was also significantly associated with SLICC (P < 0.001) and corticosteroid exposure (P = 0.017), and with age (P < 0.001), post-menopausal status (P = 0.003) and the duration of menopause (P < 0.001). Stepwise multiple linear regression analysis revealed a significant association between fat-free mass and total body, lumbar spine and femoral neck BMD (P = 0.007, P = 0.025, P = 0.003, respectively). Fat mass was significantly associated only with lumbar spine BMD (P = 0.008). In this SLE population, disease severity and corticosteroid exposure were independently associated with a negative effect both on total body BMD and on fat-free mass. Fat-free mass was a significant predictor of lumbar spine, femoral neck and total body BMD.      

Mycobacterium avium complex-associated hemophagocytic syndrome in systemic lupus erythematosus patient: report of one case

Hemophagocytic syndrome (HPS) in systemic lupus erythematosus(SLE) patients has not commonly been reported. In this case study, we report the first case of Mycobacterium avium complex (MAC)-associated hemophagocytic syndrome in a patient with systemic lupus erythematosus (SLE). This SLE patient, a 15-year-old girl, had been on a high dose of prednisolone (> 0.5mg/kg/day) for more than 3 years. She presented with a spiking fever, hepatosplenomegaly, pancytopenia, hyperferritinemia and adult respiratory distress syndrome. Bone marrow examination revealed hemophagocytosis as well as non-caseating granulomatosis. There was no indication of SLE fare-up. She responded poorly to initial treatment with methyl-prednisolone, intravenous immumoglobulin, etoposide, and drugs for Mycobacterium tuberculosis including rifampin, ethambutol, isoniazid and pyramide. However, gastric lavage culture revealed MAC. Following treatment with clarithromycin, ciprofloxacin and amikacin, her condition gradually improved and she was discharged 3 months after admission. In SLE patients with pancytopenia and hyperferritinemia, MAC-associated HPS should be considered in the differential diagnosis.     

Undifferentiated pleiomorphic sarcoma simultaneously occuring with thymoma

We report here a case of thymoma simultaneously associated with neuroendocrine tumor. A 65-year-old male, presented with cough. Radiographic studies showed a mediastinal mass. On fine needle aspiration cytology and histopathological examination, a diagnosis of thymoma with coexisting undifferentiated pleomorphic sarcoma was made. Although thymoma is associated with many extrathymic malignancies, its association with neuroendocrine tumor is rare. This case is being reported on to reinforce that clinicians should bear in mind the possibility of extrathymic malignancies in patients with thymoma.     

Malignant thymoma complicated by amegakaryocytic thrombocytopenic purpura

We report the case of a 41-year-old man with malignant thymoma complicated by amegakaryocytic thrombocytopenia 10 years after diagnosis of myasthenia gravis. A bone marrow aspirate showed an absence of megakaryocytes with normal maturation and differentiation of myeloid precursors. Three months later, severe neutropenia occurred, and a bone marrow examination confirmed the diagnosis of severe aplastic anemia. Associations between thymoma and myasthenia gravis, between thymoma and pure red cell aplasia, and between thymoma and aplastic anemia are well documented. Amegakaryocytic thrombocytopenia is not a recognized paraneoplastic syndrome complicating thymoma. Amegakaryocytic thrombocytopenia complicating thymoma may be a very early presentation of impending aplastic anemia.     

Predictors of flares and long-term outcome of systemic lupus erythematosus during combined treatment with azathioprine and low-dose prednisolone

Many patients with systemic lupus erythematosus (SLE) receive long-term treatment with azathioprine and prednisolone to control disease activity. In a retrospective study we evaluated the efficacy of combined treatment with azathioprine (2 mg/kg body weight/d) and low-dose prednisolone (7–12 mg/d) and the predictors of disease flares during this therapy regimen in 61 patients with SLE. We found three predictors of flares: renal disease, persistence of dsDNA antibodies for at least 1 year after the beginning of treatment and reduction in azathioprine dosage to below 2 mg/kg/d. The occurrence of flares was significantly associated with a higher rate of disease-related death. Furthermore, the persistence of dsDNA antibodies for at least 2 years was associated with progression of renal disease. We concluded that suppression of production of dsDNA antibodies with high avidity is a suitable parameter to determine efficacy of treatment and long-term outcome during combined therapy with azathioprine and low-dose prednisolone in SLE.     

Body composition, lipid and lipoprotein levels in childhood-onset systemic lupus erythematosus

OBJECTIVES: Systemic inflammation, corticosteroid therapy, and reduced physical activity are risk factors for altered body composition in patients with systemic lupus erythematosus (SLE). The aim of this study was to assess whether body composition differs between childhood-onset SLE patients and healthy controls, and to investigate the impact of disease characteristics and lifestyle factors on body fat mass, serum lipids, and lipoproteins. METHODS: Fat mass and lean tissue mass were measured in a cross-sectional study of 68 childhood-onset SLE patients and 68 matched healthy controls by dual-energy X-ray absorptiometry (DXA). The influence of disease, glucocorticosteroids, disease activity and severity, physical activity, and dietary intake on fat mass was evaluated by multiple linear regression analysis. Serum lipid and lipoprotein levels were measured. RESULTS: Patients had a significantly higher fat mass [mean (SD) 35.3 (10.8) vs. 30.9 (11.1)%; p = 0.024] and lower lean mass [39.7 (9.8) vs. 44.4 (1.5) kg; p = 0.003] than controls. Corticosteroid use and the disease itself were significant independent predictors of greater fat mass, while disease activity, physical activity, and dietary intake had only a minor influence. Mean high density lipoprotein (HDL) cholesterol and apolipoprotein A1 (apo A1) levels were significantly lower (p<0.001), and the mean apo B/apo A1 ratio significantly higher (p = 0.004), in patients than in controls. CONCLUSION: Childhood-onset SLE patients had a higher fat mass and lower lean mass than healthy controls and corticosteroid use was an independent predictor of increased fat mass. Patients had a more proatherogenic lipid profile, which will contribute to the increased risk of coronary heart disease in SLE patients.     

CD8+ agranular lymphocyte proliferative disorder with T-cell receptor beta-chain gene rearrangement associated with thymoma and neutropenia

A 58-year-old male with a 10-years history of thymoma was admitted to our hospital because of the respiratory infection. Hepatosplenomegaly and systemic lymphadenopathy were revealed on physical examination. Chest roentgenogram showed a large anterior mediastinal tumor and a right pleural effusion. Blood examination showed Hb 11.5 g/dl, leucocyte count 1,600/microliters (1% neutrophils, 34% monocytes, 65% lymphocytes) and platelet count 11.2 x 10(4)/microliters. The lymphocytes in the peripheral blood and pleural fluid were mostly small agranular mature lymphocytes and CD2+ 3+ 4- 8+. A monoclonal rearrangement of TCR beta chain gene was found using Southern blot analysis of the lymphocytes in the peripheral blood and pleural fluid. The CFU-GM colony formation by bone marrow cells was normal, and not suppressed by the patient's serum or peripheral blood lymphocytes. Neutrophil-associated IgG was increased with a direct immunofluorescence test. Serum IgG level was slightly decreased. Radiation therapy for thymoma exerted no effect. Treatment with prednisolone 60 mg daily resulted in complete disappearance of the pleural effusion and partial improvement of hepatosplenomegaly, thymoma and neutropenia. Histological examination of the thymoma revealed predominantly spindle cell type. He is still in good condition 21 months after diagnosis. This case seems to represent neoplastic proliferation of mature CD8+ T cells associated with thymoma.     

Three year follow-up of body composition changes in pre-menopausal women with systemic lupus erythematosus.

OBJECTIVES: To measure the change in body composition in a pre-menopausal female systemic lupus erythematosus (SLE) population over 3 yr, and to identify predictors of change in body composition including the effects of disease-, corticosteroid (CS)- and patient-related variables. METHODS: All 55 pre-menopausal females with SLE who participated in a cross-sectional study of body composition in 1994 were invited to undergo interview, examination, medical record review, and body composition assessment by dual-energy X-ray absorptiometry (DXA). RESULTS: Twenty-eight subjects participated with a mean (S.E.M.) age of 34.4 (1.6) yr, duration of SLE of 6.8 (0.8) yr and mean (range) time to follow-up of 3.2 (2.9-3.4) yr. Seventeen subjects were exposed to CS during the study period with a mean (range) daily dose of prednisolone of 12.0 (2.8-22.9) mg. There was a significant increase in body mass index (BMI) (24.53+/-0.83 vs 25.37+/-1.04, P = 0.03) and fat-free mass (41.04+/-0.83 vs 41.53+/-0.92, P = 0.05) over the 3 yr period. Univariate analysis revealed that change in fat-free mass was significantly associated with change in total body bone mineral density (BMD) (P = 0.03). Stepwise multiple linear regression analysis revealed a significant independent association of disease activity with increases in both BMI (r2 = 0.41, P = 0.006) and fat mass (r2 = 0.39, P = 0.007), and of exercise and Modified Health Assessment Questionnaire with an increase in fat-free mass (r2 = 0.51, P = 0.007). Age at SLE diagnosis and smoking were significant independent predictors for loss of total body BMD, while CS duration was predictive of an increase in total body BMD (r2 = 0.80, P < 0.0001). CONCLUSION: In this SLE population, disease activity was predictive of deleterious changes in body composition, including increases in BMI and fat mass. Patient-related variables were also important predictors of body composition change with exercise independently predicting an increase in fat-free mass, and smoking predictive of loss of total body BMD. In contrast, CS-related variables were not found to have harmful effects on body composition. Change in fat-free mass, and not fat mass, was predictive of change in total body BMD.     

Full-blown graft-versus-host disease presenting with skin manifestations,jaundice and diarrhoea: an unusual paraneoplastic phenomenon of a thymoma

We describe a patient who presented with chronic diarrhoea, skin lesions and jaundice. Based on histopathological examinations of the affected organs combined with the clinical features, it appeared that the patient fulfilled the criteria for graft-versus-host disease (GVHD). GVHD occurs especially after allogeneic stem cell transplantation and sometimes after organ transplantations. However, this patient had never undergone such a procedure. Further examination revealed that the patient also suffered from a thymoma, which was concluded to be the cause of GVHD. Unfortunately, the patient died after resection of the thymoma. This patient is probably the second case with thymoma and full-blown GVHD and shows that GVHD can occur in the absence of a previous transplantation.     

Aerobic fitness, fatigue, and physical disability in systemic lupus erythematosus

OBJECTIVE: To measure aerobic fitness, muscle strength, fatigue, and physical disability in patients with systemic lupus erythematosus (SLE). METHODS: Ninety-three patients with SLE and 41 sedentary controls were recruited into the study. Aerobic fitness was assessed by monitoring peak and submaximal oxygen uptake, heart rate, duration of exercise, and perceived exertion during a treadmill-walking test. Strength was measured using voluntary isometric quadriceps contraction. Symptomatic measures included physical and mental fatigue, mood, sleep, and functional incapacity. RESULTS: Compared to sedentary controls patients with SLE had significantly reduced levels of aerobic fitness (mean VO2peak SLE patients, 23.2 ml/kg/min vs controls, 29.6 ml/kg/min; p < 0.001) and reduced exercise capacity (mean exercise duration SLE patients, 10.4 min vs controls, 13.1 min; p < 0.001). The SLE patients also had reduced muscle strength (mean maximum voluntary quadriceps contraction SLE patients, 298 N vs controls, 376 N; p = 0.003). Resting lung function was also significantly worse in the SLE patients (mean FEV, SLE patients, 2.6 l vs controls, 2.9 l; p = 0.002). Fatigue (p < 0.001), depressed mood (p < 0.001), poor sleep quality (p < 0.001), and functional incapacity (p < 0.001) were all significantly greater in the SLE patients. Linear regression models suggested that physical disability correlated with aerobic fitness (p < 0.001), fatigue (p = 0.005), body mass index (p = 0.01), and depression (p = 0.05) and that fatigue correlated with depression (p < 0.001). CONCLUSION: Patients with SLE were less fit with reduced exercise capacity, reduced muscle strength, more fatigue, and greater disability compared to sedentary controls. Treatments developed to manage depression and improve aerobic fitness should be considered in the overall treatment of fatigue and disability in SLE.     

胸腺肿瘤的诊断和外科治疗

目的总结胸腺肿瘤的诊断和外科治疗经验。方法回顾性分析1995年至2006年人住我科手术治疗的73例胸腺肿瘤患者临床资料。结果胸部X线和CT等影像学检查是诊断木病的主要手段,重症肌无力是常见的伴随症状,单纯性胸腺瘤的治疗效果优于恶性胸腺瘤和胸腺癌。结论胸腺肿瘤是低度恶性肿瘤,手术足治疗胸腺肿瘸的主要手段。术前分期与术后放化疗是影响生存的预计因素。     

Intravenous immunoglobulin therapy in a patient with lupus serositis and nephritis

The use of intravenous immunoglobulin (IVIg) has been reported as an immunomodulating agent in several autoimmune diseases, including systemic lupus erythematosus (SLE). Herein we report a SLE patient with severe clinical presentation that included pericarditis, pleural effusion, nephrotic range proteinuria, leukopenia, and lymphopenia. The patient received one course of high-dose IVIg (2.8 g/kg body weight), and within a week of post-IVIg therapy, her condition significantly improved. One-month post-IVIg there were decreased proteinuria, elevated leukocytes and lymphocytes count, decrease in antinuclear and anti-dsDNA antibodies, and disappearance of pericarditis and pleuritis. This case demonstrates the efficacy of IVIg in severe SLE with various clinical manifestations. Received: 14 January 2000 / Accepted: 20 March 2000     

'Sustained remission' in a case of SLE following megadose cyclophosphamide

Cytotoxic therapy, especially with cyclophosphamide in the dose 8-20 mg/kg used as intermittent pulses, has been shown to improve both patient and renal survival in systematic lupus erythematosus (SLE), but to date there is no cure for the disease. Owing to the paucity of recognisable clones, the rationale and goal of cytotoxic immunosuppressive therapy in the treatment of immune-mediated diseases as against malignancies is to suppress the aberrant inflammation and immune-mediated reactions responsible for tissue damage, without dangerously suppressing the normal host defence mechanism(s). We report the case of a patient suffering from SLE with nephritis who has remained in sustained remission over the past 8 years without any maintenance therapy following an accidental administration of a single dose of 5000 mg of intravenous cyclophosphamide (44.2 mg/kg body weight). The patient recovered fully from pancytopenia following the injection. Presently, she is asymptomatic and working gainfully. Her laboratory parameters including blood counts, urine analysis, FANA and anti-dsDNA have reverted to normal. Cyclophosphamide in the dose of 30-160 mg/kg has been safely and effectively used in various neoplastic conditions with the aim of destroying every possible tumour cell. The experience of the present case suggests that such an approach may be applicable to SLE.     

Risk factors for coronary heart disease in women with systemic lupus erythematosus: the Toronto Risk Factor Study

OBJECTIVE: Because women with systemic lupus erythematosus (SLE) are 5-8 times more likely to develop coronary heart disease (CHD) than are women in the general population, we assessed the prevalence of classic risk factors for CHD in women with SLE. METHODS: Consecutive female patients with SLE who were without evidence of CHD and were attending a large lupus clinic in Toronto were studied. The control population was recruited from among age-matched subjects attending a family practice unit for an annual physical examination. The prevalence of classic CHD risk factors and the 10-year risk of a CHD-related event were determined using the Framingham risk assessment formula. Lipid subfractions, other metabolic risk factors, lifestyle variables, and demographic characteristics were also compared between the 2 groups. RESULTS: We studied 250 SLE patients and 250 controls whose mean +/- SD age was 44.8 +/- 12 years and 44.3 +/- 15 years, respectively. Hypertension and diabetes were significantly more common among the SLE patients. Although the SLE patients had a higher mean number of CHD risk factors per patient, the 10-year risk of a CHD-related event, using the Framingham multiple risk factor assessment, was the same in SLE patients and controls (3.2%). Compared with controls, SLE patients had higher levels of very low-density lipoprotein cholesterol and total triglycerides, and had higher levels of homocysteine despite having higher folate levels. Premature menopause, sedentary lifestyle, and an at-risk body habitus were also more prevalent in SLE patients. CONCLUSION: Women with SLE have a range of detectable coronary risk factors that are not fully reflected in the Framingham risk factor formula. These factors are likely to contribute to the loss of protection from CHD that has been observed in SLE.     

Pure red cell aplasia associated with thymoma

A case of thymoma with mixed spindle and lymphocytic variety along with acquired, secondary, chronic pure red cell aplasia is an uncommon entity. The presented case is a case of anterior mediastinal tumour with marked anemia. On histopathologic and hematological examinations, it proved to be a case of thymoma along with pure red cell aplasia. High index of suspicion, bone marrow examination, radiological including CT scan examination, total thymectomy after preparation with repeated blood transfusion remains the mainstay of treatment. Prolonged corticosteroid therapy leads to remission for upto ten months after operative intervention.