Malignant thymoma associated with mixed connective tissue disease: a case report

Many autoimmune diseases have been reported to be associated with malignancy. Mixed connective tissue disease (MCTD), however, has rarely been associated with malignancy. Thymoma is one of the neoplasms often reported to be related to various immunological disorders. Among the types of thymoma defined by WHO, malignant thymoma (thymoma type C) is the one least reported to be associated with autoimmune disease. Here, we report a case of malignant thymoma with concurrent MCTD, which manifested with acrosclerosis, Raynauds phenomenon, arthritis (synovitis), and a high titer of anti-ribonucleoprotein antibody.     

Ibuprofen-induced meningitis in mixed connective tissue disease

Summary A young Black woman with mixed connective tissue disease (MCTD) developed an aseptic meningitis after receiving ibuprofen. The meningeal reaction, reported infrequently in systemic lupus erythematosus (SLE) and only once previously in MCTD, was characterized by a predominantly polymorphonu-clear cerebrospinal fluid (CSF) pleocytosis and depression of CSF glucose. Reversible renal insuffiency also occurred. Features suggestive of a hypersensitivity reaction included pruritus, conjunctivitis, facial oedema, desquamation of the palms and soles, and subsequent near total alopecia. Meningeal signs responded rapidly to systemic corticosteroid therapy. Patients with MCTD as well as those with SLE may be at peculiar risk of developing this uncommon reaction to ibuprofen.     

Panniculitis in a patient with mixed connective tissue disease

A 51-year-old woman who had been suffering from mixed connective tissue disease (MCTD) for 8 years developed an erythematous rash with pain and tenderness on her left leg. A skin biopsy revealed septal panniculitis with multiple lymphangiectasis. No vasculitis was observed. An increase in her prednisolone dose from 5mg to 20mg/day led to an improvement in these lesions. Panniculitis is very rare in MCTD. The clinical significance of panniculitis in MCTD is also discussed.     

Rheumatoid factor isotypes in mixed connective tissue disease

Mixed connective tissue disease (MCTD) is a connective tissue disorder that is often accompanied by various immunological abnormalities. In this study, we analyzed serum levels of rheumatoid factor (RF) isotypes in patients with MCTD and in normal controls to determine if any of these isotypes reflects the severity of the disease. IgM-RF, IgG-RF, and IgA-RF were positive in 48, 38, and 33% of the patients, respectively. The frequency of positive anti-SS-A antibody and decrease in white blood cell counts were significantly greater in patients with elevated IgA-RF levels than that in those with normal levels. These results suggest that the presence of RF isotypes can be regarded as one of the various immunological abnormalities of MCTD.     

Thrombotic thrombocytopenic purpura occurring in a patient with mixed connective tissue disease

Summary A case of thrombotic thrombocytopenic purpura (TTP) occurring in a patient with mixed connective tissue disease (MCTD) is reported.     

Meningitis in mixed connective tissue disease complicated by herpes virus infection: case report

The authors report a rare case of a female patient diagnosed with mixed connective tissue disease (MCTD). After a few years in remission, the patient acquired herpes zoster infection followed by a disease flare. Disease activity was accompanied by the development of meningitis. To determine whether the meningitis was caused by the previous herpes virus infection or was aseptic meningitis associated with the activity of MCTD raised important differential diagnostic issues. Repeated laboratory assessments of the patients sera and cerebrospinal fluid revealed leukocytopenia, high anti-U1 ribonucleoprotein autoantibody level, increased immune complex, and decreased complement concentrations. The administration of corticosteroids resulted in rapid improvements in clinical symptoms and laboratory indicators.     

Osteoporosis in mixed connective tissue disease

The existence of osteoporosis in 58 postmenopausal women with mixed connective tissue disease (MCTD) was investigated. The mean bone mineral density assessed by dual energy X-ray absorptiometry in the lumbar spine was decreased in 25.8% of the patients, reflecting osteoporosis (T score < –2.5). In the femoral neck there was no significant difference between the BMD of MCTD patients and that of age-matched, healthy postmenopausal women. Low bone mineral density was found among patients on, as well as off, corticosteroids. The extent of bone loss was associated with disease duration, as well as corticosteroid therapy. Serum osteocalcin levels were lower in MCTD patients than in controls. Lower serum oestradiol, testosterone and dehydroepiandrosterone sulphate levels were detected in MCTD patients than in controls. Thus, MCTD may be associated with increased bone loss. Pathogenic factors may include the disease itself, corticosteroid therapy, impaired osteoblast function, and low serum sex hormone levels.     

Necrotizing fasciitis caused by Streptococcus pneumoniae in mixed connective tissue disease

A 42-year-old man was hospitalized because of chills, fever, and severe polyarthralgia. He had a 5-year history of mixed connective tissue disease (MCTD) with polyarthritis which had been treated with a nonsteroidal anti-inflammatory drug alone. On the second day of hospitalization, necrotizing fasciitis of the right leg developed. Streptococcus pneumoniae was later detected in a blood culture. Pneumococcal infections of the soft tissues are uncommon, and have been reported in immunosuppressed patients and patients with systemic lupus erythematosus. This is the first report of a case of necrotizing fasciitis caused by S. pneumoniae in a patient with MCTD. Received: December 1, 1999 / Accepted: April 21, 2000     

A case of mixed connective tissue disease complicated with hypertrophic obstructive cardiomyopathy

A 54-year-old female was diagnosed as mixed connective tissue disease (MCTD) complicated with secondary Sj?gren's syndrome. Although she had no dyspnea on exertion, the chest X-ray showed cardiomegaly with interstitial pneumonia. The echocardiogram demonstrated asymmetric hypertrophy of the interventricular septum. Diagnosis of hypertrophic obstructive cardiomyopathy (HOCM) was confirmed by left ventriculography and myocardial biopsy. She was treated with prednisolone, resulting in improvement of swollen hand, elevated muscle enzymes and interstitial pneumonia. A rare complication of HOCM with MCTD was described.     

Pulmonary arterial hypertension in mixed connective tissue disease: successful treatment with Iloprost

This paper describes a 61-year-old woman who presented with mixed connective tissue disease, which was complicated by the development of pulmonary arterial hypertension (PAH). Her condition worsened rapidly, with development of haemopthysis, tachypnoe and cardiac arrest. Doppler echocardiography showed a high systolic pulmonary arterial pressure (98 mmHg), confirmed by the right heart catheterization. Vasculopathy of the pulmonary artery vessels was detected following open lung biopsy. No pulmonary embolism was found. Because of suspicion of flare of her underlying disease, which leads to PAH, immunosuppressive treatment was started with high doses of corticosteroid and cyclophosphamide, in combination with the prostacyclin analogue, Iloprost, and low molecular weight heparin. The therapy resulted in slow recovery over 6 weeks, with control echocardiography showing normalization of the high pulmonary pressure, and the patient being capable of returning to everyday activities.     

Pulmonary veno-occlusive disease as a primary cause of pulmonary hypertension in a patient with mixed connective tissue disease

Mixed connective tissue disease (MCTD) is a systemic disease seen in a group of patients with overlapping clinical features of lupus, scleroderma, polymyositis, and rheumatoid arthritis. A defining feature of MCTD is the presence of antibodies against the U1-ribonucleoprotein (U1-RNP) complex. Pulmonary hypertension is the major cause of death in MCTD. We report an autopsy case of MCTD with pulmonary hypertension. The U1-RNP antibody of this patient was 171.9 U (normal < 25.0 U). The immediate cause of death was attributed to acute pulmonary embolism at left lower lobe. A severe vasculopathy characterized by fibrotic occlusion of small veins and venules, associated with prominent capillary congestion, was consistent with pulmonary veno-occlusive disease (PVOD). This is the first case reported in which PVOD is the primary cause of pulmonary hypertension in MCTD.     

A case of mixed connective tissue disease complicated with thymic carcinoma and Hashimoto's thyroiditis

We report the case of a 63-year-old woman who suffered from mixed connective tissue disease (MCTD) complicated with thymic carcinoma and Hashimoto's thyroiditis. Although many systemic syndromes associated with thymoma and thymic carcinoma, i.e., myasthenia gravis, pure red cell aplasia, hypogammaglobulinemia, and Hashimoto's thyroiditis, are known, this is the first report of MCTD complicated with thymic carcinoma. It was suggested that MCTD may be a paraneoplastic syndrome associated with thymic carcinoma.     

Diastolic function of the heart in mixed connective tissue disease

The authors examined the right and left ventricle functions in patients with mixed connective tissue disease (MCTD) by Doppler echocardiography. Of 51 patients, 20 had temporary pulmonary arterial hypertension in their case history. According to our knowledge, this is the first study examining the use of Doppler echocardiography and tissue Doppler technique in MCTD patients. Of 51 MCTD patients, 20 had pulmonary arterial hypertension (PAH) in the past 2 years. Diameters of the right and left ventricle, systolic and diastolic blood pressure were measured both in the 51 MCTD patients and in the 30 control subjects (mean age 54.8±6.2 years in the case of patients and 54.2±8.8 years in the case of control subjects). To estimate the global ventricle functions, the myocardial performance index—as described by Tei et al. (J Am Soc Echocardiogr 6:838–874, 1996)—was applied, which reflects the ratio of the sum of the isovolumetric contraction and relaxation time as compared to the ejection time. The 20 MCTD patients with PAH received cyclophosphamide therapy for 1 year beside the pulse corticosteroid (CS) therapy. In the case of MCTD patients without PAH, different treatments were used: 12 out of 31 patients were treated with sulfasalazine, 5 of whom received a combination of CS and methotrexate, and 14 took nonsteroid antiinflammatory drugs. In the case of the 51 MCTD patients (20 with PAH and 31 without PAH), diastolic function disorder of the left ventricle was detected; the diastolic E _e/A _a velocity quotient of the lateral mitral anulus was lower (p<0.01), and the mean deceleration time was longer (p<0.001) than that of the control group. The Tei index demonstrated the damage of the global ventricle function. The Tei index of the right ventricle indicated global failure of the right ventricle function in the case of MCTD patients complicated with PAH (Tei index 0.36±0.07 in MCTD with PAH and 0.28±0.04 in MCTD without PAH, p<0.001). The right ventricle function of MCTD patients without PAH was no different from that of the control group. In the case of patients with MCTD, signs of the disorder of the left ventricle diastolic function were observed. Our results suggest that the global impairment of the left ventricle function is the consequence of the disease itself and not the side effect of the treatment. In the case of MCTD patients complicated with PAH, the signs of the right ventricle function impairment proved to be permanent.     

A case of mixed connective tissue disease presenting with nephrotic syndrome

Abstract

A 70-year-old woman was admitted to our hospital for the treatment of diffuse scleroderma and marked edema in the lower extremities. Renal biopsy revealed membranous change, interstitial nephritis, and intimal hyperplasia of the small arteries. The patient was diagnosed as having mixed connective tissue disease (MCTD) presenting with nephrotic syndrome (NS). She responded well to a combination treatment consisting of methylprednisolone (m-PSL) pulse therapy, oral PSL, and cyclosporine A (CsA). We speculated on the actual pathogenesis of NS in this case of MCTD.     

A case of mixed connective tissue disease presenting with nephrotic syndrome

A 70-year-old woman was admitted to our hospital for the treatment of diffuse scleroderma and marked edema in the lower extremities. Renal biopsy revealed membranous change, interstitial nephritis, and intimal hyperplasia of the small arteries. The patient was diagnosed as having mixed connective tissue disease (MCTD) presenting with nephrotic syndrome (NS). She responded well to a combination treatment consisting of methylprednisolone (m-PSL) pulse therapy, oral PSL, and cyclosporine A (CsA). We speculated on the actual pathogenesis of NS in this case of MCTD.     

血清肌钙蛋白与结缔组织疾病损伤心脏的相关研究

目的 探讨血清肌钙蛋白Ｉ（ｔｒｏｐｏｎｉｎ,Ｉ,Ｔｎ－Ｉ）、肌钙蛋白Ｔ（ｔｒｏｐｏｎｉｎＴ,Ｔｎ－Ｔ）与结缔组织疾病ｃｏｎｎｅｃｔｉｖｅ ｔｉｓｓｕｅ ｄｉｓｅａｓｅｓ,ＣＴＤ）损伤心脏的关系。方法 本实验以酶联免疫吸附法（ＥＬＩＳＡ）检测了９９例ＣＴＤ患者的血清Ｔｎ－Ｉ、Ｔｎ－Ｔ浓度,与正常对照组进行了比较,其阳性率与ＣＫ－ＭＢ、ＵＣＧ、ＥＣＧ阳性率进行了比较。结果 ９９例ＣＴＤ患者,其中系统性     

Sarcoidosis in patients with mixed connective tissue disease: clinical, genetic, serological and histological observations

The objective of this study was to investigate how the development of sarcoidosis influences the disease course of mixed connective tissue disease (MCTD). The cellular composition of MCTD-associated sarcoidosis granulomas was evaluated and also the disease-accompanying T-cell activation and alterations of the serum cytokine levels were measured before and after the therapy. The HLA-DR specific alleles were also assessed. We present two cases with MCTD coexisting sarcoidosis. Serum concentrations of Th1 and Th2 cytokines were assessed by ELISA. Peripheral blood CD3+ total T-cell numbers, CD4+ and CD8+ T-cell subset were determined by flow cytometry. Furthermore, hematoxylin-eosin staining and immunhistochemistry were performed for histological assessment. HLA-DR specific alleles were determined by using PCR-SSP. Elevated number of activated T-cells and high Th1 cytokine levels were detected, mainly IFN-gamma and TNF-alpha. Histologically, CD4+ and CD8+ T-cells were present in the sarcoidosis infiltrations. The haplotypes were to some extent dissimilar from the HLA-DR genotype from patients with MCTD, or sarcoidosis alone. Sarcoidosis enhances the activation of MCTD, based on the laboratory and clinical findings. Our results show that the inflammation is mainly in the effector phase, while granuloma formation is characteristic of the resolution phase of the disease. The assessment of the cytokine network in sarcoidosis-associated MCTD enables us to select the most effective, individualized therapy protocol for these patients.     

Aggressive autoimmune hepatitis in a case of mixed connective tissue disease

The association of autoimmune hepatitis and mixed connective tissue disease (MCTD) has rarely been described in the literature. We report a 16‐year‐old female patient with established diagnosis of MCTD who developed autoimmune hepatitis in 2006 1 year after her disease onset. The diagnosis of autoimmune hepatitis in our case was based on elevated liver enzymes, positive anti‐nuclear antibody, positive anti‐smooth muscle antibody (ASMA), positive liver‐kidney microsomal antibody (anti–LKM‐1) and negative virology screening tests for viral hepatitis. The patient as successfully treated with steroid and azathioprin.     

Case of mixed connective tissue disease associated with autoimmune hepatitis

Summary A 56-year-old female with mixed connective tissue disease (MCTD) who developed autoimmune hepatitis is described. Hepatitis was controlled effectively by the corticosteroid therapy. Biopsy of the liver revealed swelling and hydropic degeneration of hepatocytes, accompanied by Councilman's body formation and focal necrosis. These histological findings differ from those in three previously described cases. A relationship between MCTD and liver involvement appears possible.