Clinical Features of Systemic Sclerosis-Mixed Connective Tissue Disease and Systemic Sclerosis Overlap Syndromes.

OBJECTIVE: To describe the clinical characteristics and outcomes of systemic sclerosis-mixed connective tissue disease (SSc-MCTD) and SSc overlap syndrome. METHODS: We included patients from the Australian Scleroderma Cohort Study who met American College of Rheumatology/European Alliance of Associations for Rheumatology criteria for SSc. Three mutually exclusive groups were created: SSc-MCTD, SSc overlap, and SSc only. Univariate comparison of clinical features was performed by analysis of variance or chi-square test. Survival analysis was performed using Kaplan-Meier (KM) curves and Cox proportional hazards regression models. RESULTS: Of 1,728 patients, 97 (5.6%) had SSc-MCTD, and 126 (7.3%) had SSc overlap. Those with MCTD-SSc were more commonly Asian (18.3% versus 10.1% in SSc overlap, and 3.6% in SSc only; P < 0.0001) and younger at disease onset (38.4 years versus 46.5 or 46.8 years, P < 0.0001). Those with SSc-MCTD or SSc overlap were more likely to have limited cutaneous SSc. All 3 groups had similar frequency of interstitial lung disease (ILD), although pulmonary arterial hypertension (PAH) was less common in SSc overlap. Synovitis and myositis were more common in SSc overlap and SSc-MCTD than in SSc only. KM curves showed better survival in SSc-MCTD than SSc overlap or SSc only (P = 0.011), but this was not significant after adjustment for sex and age at disease onset. SSc-specific antibodies were survival prognostic markers, with antinuclear antibody centromere or anti-RNP conferring better survival than anti-Scl-70 or anti-RNA polymerase III (P = 0.005). Patients with SSc-MCTD and SSc overlap had lower mortality following diagnosis of ILD and PAH than patients with SSc only. CONCLUSION: This study provides insights into the clinical characteristics of patients with SSc-MCTD, SSc overlap, and SSc only and shows that anti-RNP antibodies are associated with better survival than anti-Scl-70 and anti-RNA polymerase III antibodies.

Worldwide trends in all-cause mortality of auto-immune systemic diseases between 2001 and 2014.

AIM: To describe changes in the 2001-2014 mortality of 6 autoimmune systemic diseases (AISDs), namely Systemic Lupus Erythematosus (SLE), Systemic Sclerosis (SSc), Idiopathic Inflammatory Myopathies (IIM), Sjögren's Syndrome (SS), Mixed Connective Tissue Disease (MCTD) and ANCA-associated vasculitis (AAV) at the country-, continent-, and world-levels. METHODS: Mortality data were retrieved from the World Health Organization (WHO) mortality database for each disease, based on ICD-10 codes. We computed age-standardized mortality rate (ASMR) as the estimated number of deaths per million inhabitants and its 95% confidence interval (95%CI). The association between gender, geographical areas and disease-specific mortality was analyzed using multivariate Poisson regression. The 2001-2014 temporal trends were analyzed using Jointpoint software. RESULTS: In 2014, the worldwide ASMR for SLE was 2.68 (95%CI: 2.62-2.75) deaths/millions inhabitants, 1.46 (1.42-1.51) for SSc, 0.47 (0.44-0.49) for IIM, 0.17 (0.15-0.18) for SS, 0.11 (0.10-0.13) for MCTD and 0.53 (0.50-0.56) for AAV, with ASMRs generally lower in Europe than in North America, Latin America and Asia. Between 2001 and 2014, the worldwide ASMR decreased significantly for SSc (-0.71%/year), IIM (-1.65%/year) and AAV (-1.01%/year; p < .001 for all) and increased for SS (+1.53%/year, p = .01). The worldwide ASMR of SLE decreased significantly between 2001 and 2003 (-6.37%, p < .05) before increasing slightly between 2004 and 2014 (+0.58%, p < .01). CONCLUSIONS: We observed a strong heterogeneity of standardized mortality rates across all countries analyzed for 6 autoimmune diseases. Those results further highlight the impact of world-wide inequities and major gaps in access to care and strategies for diagnosis and management of rare diseases, a crucial finding for world-wide physicians, patient associations and policy makers.

"Mixed connective tissue disease": a condition in search of an identity.

Mixed connective tissue disease was first described as a new autoimmune rheumatic disease in 1972 based on the claim of a distinct clinical picture associated with anti-RNP antibody positivity. Subsequently, this new entity has divided opinions in the rheumatology community. We have reviewed recent cohort studies with more than 100 patients, comparing the clinical and immunological features, treatment, prognosis and evolution to well-defined autoimmune rheumatic diseases. We also reviewed clinical features of undifferentiated autoimmune rheumatic diseases based on the most recent studies. After gathering and reviewing these data, we discuss whether the designation "mixed connective tissue disease" should be maintained.

Facts and controversies in mixed connective tissue disease. / Hechos y controversias en la enfermedad mixta del tejido conectivo.

Mixed connective tissue disease (MCTD) is a systemic autoimmune rheumatic disease (SARD) characterised by the combination of clinical manifestations of systemic lupus erythematosus (SLE), cutaneous systemic sclerosis (SSc) and polymyositis-dermatomyositis, in the presence of elevated titers of anti-U1-RNP antibodies. Main symptoms of the disease are polyarthritis, hand oedema, Raynaud's phenomenon, sclerodactyly, myositis and oesophageal hypomobility. Although widely discussed, most authors today accept MCTD as an independent entity. Others, however, suggest that these patients may belong to subgroups or early stages of certain definite connective diseases, such as SLE or SSc, or are, in fact, SARD overlap syndromes.

Associations between circulating endostatin levels and vascular organ damage in systemic sclerosis and mixed connective tissue disease: an observational study.

INTRODUCTION: Systemic sclerosis (SSc) and mixed connective tissue disease (MCTD) are chronic immune-mediated disorders complicated by vascular organ damage. The aim of this study was to examine the serum levels of the markers of neoangiogenesis: endostatin and vascular endothelial growth factor (VEGF), in our unselected cohorts of SSc and MCTD. METHODS: Sera of SSc patients (N = 298) and MCTD patients (N = 162) from two longitudinal Norwegian cohorts were included. Blood donors were included as controls (N = 100). Circulating VEGF and endostatin were analyzed by enzyme immunoassay. RESULTS: Mean endostatin levels were increased in SSc patients 93.7 (37) ng/ml (P < .001) and MCTD patients 83.2 (25) ng/ml (P < .001) compared to controls 65.1 (12) ng/ml. Median VEGF levels were elevated in SSc patients 209.0 (202) pg/ml compared to MCTD patients 181.3 (175) pg/ml (P = .017) and controls 150.0 (145) pg/ml (P < .001). Multivariable analysis of SSc subsets showed that pulmonary arterial hypertension (coefficient 15.7, 95 % CI: 2.2-29.2, P = .023) and scleroderma renal crisis (coefficient 77.6, 95 % CI: 59.3-100.0, P < .001) were associated with elevated endostatin levels. Multivariable analyses of MCTD subsets showed that digital ulcers were associated with elevated endostatin levels (coefficient 10.5, 95 % CI: 3.2-17.8, P = .005). The risk of death increased by 1.6 per SD endostatin increase (95 % CI: 1.2-2.1, P = .001) in the SSc cohort and by 1.6 per SD endostatin increase (95 % CI: 1.0-2.4, P = .041) in the MCTD cohort after adjustments to known risk factors. CONCLUSIONS: Endostatin levels were elevated in patients with SSc and MCTD, particularly SSc patients with pulmonary arterial hypertension and scleroderma renal crisis, and MCTD patients with digital ulcers. Elevated endostatin levels were also associated with increased all-cause mortality during follow-up in both groups of patients. We propose that endostatin might indicate the degree of vascular injury in SSc and MCTD patients.

Clinical course, prognosis, and causes of death in mixed connective tissue disease.

OBJECTIVE: To study the survival rate and prognostic indicators of mixed connective tissue disease (MCTD) in a Hungarian population. METHODS: Two hundred eighty patients with MCTD diagnosed between 1979 and 2011 were followed prospectively. Clinical features, autoantibodies, and mortality data were assessed. Prognostic factors for survival were investigated and survival was calculated from the time of the diagnosis by Kaplan-Meier method. RESULTS: A total of 22 of 280 patients died: the causes of death were pulmonary arterial hypertension (PAH) in 9 patients, thrombotic thrombocytopenic purpura in 3, infections in 3, and cardiovascular events in 7. The 5, 10, and 15-year survival rates after the diagnosis was established were 98%, 96%, and 88%, respectively. The deceased patients were younger at the diagnosis of MCTD compared to patients who survived (35.5 ± 10.4 vs 41.8 ± 10.7 yrs; p < 0.03), while there was no difference in the duration of the disease (p = 0.835). Our cohort study showed that the presence of cardiovascular events (p < 0.0001), esophageal hypomotility (p = 0.04), serositis (p < 0.001), secondary antiphospholipid syndrome (p = 0.039), and malignancy (p < 0.001) was significantly higher in the deceased patients with MCTD. The presence of anticardiolipin (p = 0.019), anti-ß2-glycoprotein I (p = 0.002), and antiendothelial cell antibodies (p = 0.002) increased the risk of mortality. CONCLUSION: Overall, PAH remained the leading cause of death in patients with MCTD. The prevalence of cardiovascular morbidity and mortality, malignancy, and thrombotic events increased during the disease course of MCTD. The presence of antiphospholipid antibodies raised the risk of mortality.

Distinct phenotypes in mixed connective tissue disease: subgroups and survival.

The aim of the present study was to assess the autoantibody profile, dominant clinical symptoms and cluster characteristics of different mixed connective tissue disease (MCTD phenotypes. Two-hundred-and-one patients with MCTD were followed-up longitudinally. Five clinical parameters, Raynaud's phenomenon, pulmonary artery hypertension (PAH), myositis, interstitial lung disease (ILD), erosive arthritis and five auto-antibodies besides anti-U1RNP, antiendothelial cell antibodies (AECA), anti-CCP, anti-cardiolipin (anti-CL), anti-SSA/SSB and IgM rheumatoid factor (RF) were selected for cluster analysis. The mean age of patients was 52.9 ± 12.4 years and the mean follow-up of the disease was 12.5 ± 7.2 years. Patients were classified into three cluster groups. Cluster 1 with 77 patients, cluster 2 with 79 patients and cluster 3 with 45 patients. In cluster 1 the prevalence of PAH (55.8%; p < 0.001), Raynaud's phenomenon (92.2%; p < 0.001) and livedo reticularis (24.6%, p < 0.001) was significantly greater than in cluster 2 and 3. In cluster 2, the incidence of ILD (98.7%; p < 0.001), myositis (77.2%; p < 0.001), and esophageal dysmotility (89.8%; p < 0.001) was significantly greater than that in cluster 1 and 3. In cluster 3, anti-CCP antibodies were present in 31 of 45 patients (68.8%) with erosions. Anti-CCP antibodies were present in 37 of 42 patients (88.0%) with erosions. PAH, angina, venous thrombosis was observed in cluster 1 and pulmonary fibrosis in cluster 2, musculosceletal damage, gastrointestinal symptoms and osteoporotic fractures were most frequent in cluster 3. Cumulative survival assessment indicated cluster 1 patients having the worst prognosis. Cluster analysis is valuable to differentiate among various subsets of MCTD and useful prognostic factor regarding the disease course.

Prevalence and severity of interstitial lung disease in mixed connective tissue disease: a nationwide, cross-sectional study.

BACKGROUND: Mixed connective tissue disease (MCTD) is an immune-mediated, systemic disorder of unknown cause. OBJECTIVE: To assess the prevalence, pattern and severity of interstitial lung disease (ILD) in a cross-sectional study of the nationwide, Norwegian MCTD cohort. METHODS: 126 patients with MCTD were systematically examined for ILD by high-resolution CT (HRCT), pulmonary function tests (PFT), 6 min walk test (6MWT) and by the New York Heart Association (NYHA) functional classification of dyspnoea. The extent and type of HRCT lung abnormalities were scored according to the CT criteria of ILD recommended by the Fleischner Society. RESULTS: All 126 patients were Caucasian, 75% women. At the time of the cross-sectional ILD study, the patients had a mean disease duration of 9.0 years. 52% of the patients had abnormal HRCT findings, most commonly reticular patterns consistent with lung fibrosis (35%). Lung fibrosis was quantified as minor in 7%, moderate in 9% and severe in 19% of the patients. Fibrosis was uniformly concentrated in the lower parts of the lungs and was not associated with smoking. Patients with severe lung fibrosis had lower PFT values, shorter 6MWT and a higher mean NYHA functional class. After a mean 4.2 years' follow-up, overall mortality was 7.9%. Mortality in patients with normal HRCT was 3.3%, as compared with 20.8% in patients with severe lung fibrosis (p<0.01). CONCLUSIONS: Severe lung fibrosis is common in MCTD, has an impact on pulmonary function and overall physical capacity and is associated with increased mortality.

Muerte súbita en un joven con Síndrome de Marfan / Sudden death in a young man with Marfan´s Syndrome

El síndrome de Marfan es un trastorno del tejido conectivo con grados de expresión clínica variable. Las manifestaciones clínicas más importantes de este síndrome suelen localizarse a nivel ocular, esquelético y cardiovascular, siendo estas últimas las que con mayor frecuencia conducen a la muerte. Las complicaciones cardiovasculares se presentan principalmente a nivel valvular y aórtico; en concreto a este último nivel es común observar áreas de degeneración quística de la capa media de la aorta (medionecrosis quística), caracterizada por la presencia de apoptosis y por la pérdida de células musculares lisas. Aunque el sustrato biológico específico es desconocido, se ha atribuido a la existencia de un aumento en la síntesis de ácido hialurónico, un aumento en la solubilidad del colágeno y de la elastina, alteraciones en la cantidad relativa de colágeno tipo I y III y más recientemente la presencia de cadenas de colágeno-alfa2. El interés de este cuadro en Patología forense radica en su posible presentación en forma de muerte súbita sin ningún tipo de clínica previa. Resulta por tanto fundamental identificar cuidadosamente todos los hallazgos necrópsicos para poder relacionarlos con este síndrome. La cuestión posee además un interés epidemiológico al objeto de comunicar a la familia del fallecido aquella información que sea de importancia médica para otros miembros de la misma. Exponemos un caso de estas características en un varón joven, sin patología previa conocida que falleció súbitamente a la salida de una discoteca. El estudio necrópsico reveló una disección aórtica en su porción extrapericárdica como causa responsable de la muerte. El caso se ilustra además con el correspondiente estudio histopatológico específico

Marfan´s syndrome is a disorder of the connective tissue with a variable clinical expression. Clinically the most important manifestations are the ocular, skeletal and cardiovascular ones, which frequently lead to death. Cardiovascular complications involve mainly the valves and the aorta, in fact at this level is common finding cystic medial degeneration areas, characterized by apoptosis and by the loss of vascular smooth muscle cells. Although the specific biological defect is unknown, it has been thought to be an increase of the hialuronic acid synthesis, an increase of the collagen and elastine solubility, the alteration in the ratio collagen type-1 and type-3 and more recently, the presence of collagen-alpha2 chains. The interest of this syndrome in forensic pathology is that it can be present as a sudden death without any previous manifestation, being very important to identify carefully all the autopsy findings to relate them with this syndrome. It has also an epidemiologic interest with the aim of communicating the information that may be of medical importance to other family´s members. We report a case with these characteristics in a young man without previous symptoms who died suddenly at the disco´s exit. The macroscopic examination showed aortic dissection in the extrapericardical portion, considered as cause of the death. The case is also illustrated with the specific histopathologic study

The prognosis of mixed connective tissue disease.

The prognosis for patients who have mixed connective tissue disease (MCTD) varies from a benign course to severe progressive disease. In approximately one third of patients the clinical symptoms go into long-term remission and the anti-U1 small nuclear ribonucleoprotein antibodies disappear. One third of patients have a severe, progressive disease course. Persistent morbidity often is attributable to arthritis, easy fatiguability, and dyspnea on exertion. The most severe clinical manifestation is pulmonary hypertension which contributes to premature death in patients who have MCTD. Pulmonary hypertension is associated with proliferative vascular abnormalities that involve small pulmonary vessels, rather than interstitial lung disease.

[Evaluation of survival in mixed connective tissue disease (MCTD)]. / Túlélés kevert kötószöveti betegségben (MCTD).

INTRODUCTION: 179 patients with mixed connective tissue disease (MCTD) were follow-up, and the cause of death was analyzed in 12 died patients. PATIENTS AND METHODS: The survival of 179 patients with MCTD was evaluated by using Kaplan-Meier's method. Clinically and immunological data of the patients were analyzed between 1 and 25 years follow-up period (mean: 13.1 +/- 5.5 years). RESULTS: The five-year survival rate was 96.4%, 10-year survival rate was 93.9%, and the 15-year survival rate was 89.6%. The cause of death was pulmonary hypertension in 5 patients, thrombotic thrombocytopenic purpura/hemolytic uremic syndrome in 3 cases, infection in 3 cases (hepatitis C virus induced hepatic coma in 2 patients, Staphylococcus sepsis in one patient), and on one patient myocarditis. The pulmonary hypertension was the most serious prognostic factor. CONCLUSION: In patients with MCTD the pulmonary hypertension with endothelial cells proliferation and microangiopathy developed very quickly, and there was progressive and therapy resistant statement. The secondary virus and bacterial infections may develop in the patients who were followed-up the long term period. Their survival rate was better than the data in the literature. This fact may cause genetic-demographic factors, and the sequential follow-up of the patients.

The impact of coexisting connective tissue disease on survival in patients with fibrosing alveolitis.

OBJECTIVES: Previous reports have suggested that patients who have fibrosing alveolitis in association with a connective tissue disease (FA-CTD) have a better prognosis than patients with 'lone' cryptogenic fibrosing alveolitis (LCFA). The present study was designed to compare the survival of a general population-based sample of patients with FA-CTD and LCFA both with each other and with the general population. METHODS: A survival analysis was performed using data for 107 patients with FA-CTD, 872 with LCFA and 5958 controls matched for age, sex and general practice, drawn from the General Practice Research Database. The data were analysed using Cox regression, adjusting for a number of potential confounders, including age, gender, smoking habit and use of oral corticosteroids. RESULTS: The median follow-up period was 2.1 yr and during this time 54 (50%) patients with FA-CFA, 386 (44%) patients with LCFA and 601 (10%) controls died. The mortality rates for patients with FA-CTD, LCFA and the controls were 284, 270 and 41 per 1000 person-yr respectively. After adjusting for age, gender, smoking habit and exposure to oral corticosteroids, patients with FA-CTD had a marginally worse survival than patients with LCFA (hazard ratio 1.20, 95% confidence interval 0.90-1.61). Compared with the general population controls, patients with either LCFA or FA-CTD had a considerably worse prognosis (hazard ratio 5.56, 95% confidence interval 4.77-6.49). CONCLUSIONS: The median survival in patients with fibrosing alveolitis is less then 3 yr. We found no evidence to support previous reports of a better prognosis amongst patients with FA-CTD.

Long-term outcome in mixed connective tissue disease: longitudinal clinical and serologic findings.

OBJECTIVE: To determine the long-term clinical and immunologic outcomes in a well-characterized cohort of 47 patients with mixed connective tissue disease (MCTD), including reactivity with U small nuclear RNP (snRNP) polypeptides. METHODS: Patients were followed up over a period of 3-29 years with immunogenetic and systematic clinical and serologic analysis. Sera were analyzed for reactivity with snRNP polypeptides U1-70 kd, A, C, B/B', and D, for anti-U1 RNA, and for anticardiolipin antibodies (aCL). RESULTS: The typical core clinical features of MCTD tended to develop over time; features of inflammation as well as Raynaud's phenomenon and esophageal hypomotility diminished, while pulmonary hypertension, pulmonary dysfunction, and central nervous system disease persisted, following treatment. A favorable outcome was observed in 62% of patients; 38% had continued active disease or had died, with death associated with pulmonary hypertension and aCL. All patients had autoantibodies to the U1-70 kd polypeptide of snRNP, and most were positive for anti-U1 RNA. An orderly progression of intramolecular spreading of autoantibody reactivity against snRNP polypeptides was observed, as was the novel finding of "epitope contraction" followed by disappearance of anti-snRNP autoantibodies during prolonged remission. CONCLUSION: These patients demonstrated the typical immunogenetic, clinical, and serologic findings of MCTD, and the condition rarely evolved into systemic lupus erythematosus or systemic sclerosis. The majority of patients had favorable outcomes, with pulmonary hypertension being the most frequent disease-associated cause of death. Intramolecular spreading of autoantibody reactivity against snRNP polypeptides was observed, followed by "epitope contraction" and ultimate disappearance of anti-snRNP autoantibodies during prolonged disease remission.

Clinical features of patients with juvenile onset mixed connective tissue disease: analysis of data collected in a nationwide collaborative study in Japan.

OBJECTIVE: To analyze the clinical features and outcome of juvenile-onset mixed connective tissue disease (MCTD). METHODS: Clinical and laboratory findings were compared in 2 groups of MCTD patients divided according to age at onset: juvenile onset: under 16 yrs: adult onset: 16 yrs or older). RESULTS: Systemic lupus erythematosus-like symptoms, such as facial erythema, photosensitivity. LE cells, lymphadenopathy, and cellular casts, were more frequent in juvenile onset MCTD than in the adult form of the disease. On the other hand, scleroderma-like symptoms, such as esophageal hypomotility, scleroderma-like lesions evident on skin biopsy, pulmonary involvement, proximal scleroderma, and pitting scars, were less frequent in juvenile onset MCTD than in the adult form. Patients with juvenile onset MCTD more frequently met the classification criteria for systemic lupus erythematosus (SLE) and less frequently met those for progressive systemic sclerosis (SSc), compared to patients with adult onset MCTD. At disease onset, hand edema and stiffness were observed less frequently in juvenile onset MCTD than in the adult form. Furthermore, the mortality rate was lower in the former than in the latter (2.8% vs 8.4%). CONCLUSION: Although previous studies have reported severe symptoms and adverse outcome for juvenile onset MCTD, we conclude from this nationwide study in Japan that patients with juvenile onset MCTD exhibit more SLE-like and fewer SSc-like features and have a relatively favorable outcome.

Mixed connective tissue disease. A clinico-serological study of 17 cases.

Mixed connective tissue disease (MCTD) was described as a distinct clinical syndrome in 1972. Since then many cases have been reported in the literature worldwide. In this study we present our experience with a group of 17 Mexican patients with this syndrome, and we analyze their clinical and serological features, as well as the causes of death in these patients. The patients are Mexican mestizos living in Guadalajara and most of them have been followed-up at Hospital General de Occidente for a period of 1-10 years. The female/male ratio was 16:1, and their age ranged from 14-55 years with a mean of 29 years. The disease duration has ranged from 1-17 years, with a mean of 6 years. Among the clinical manifestations we have found a high frequency of lymphadenopathy when compared with published series (13/17 or 76%), and the laboratory findings in our patients included a very high polyclonal increase of gammaglobulins (93%), lymphopenia (76%), direct immunofluorescence speckled nuclear epidermal deposits in skin biopsies (75%) and positive rheumatoid factor (65%). Other clinical and serological features were similar to those reported in other series of patients with MCTD. Six of the 17 patients have died (35%), and in 3 of them (17.5%) the cause of death was due to an infectious disease that suddenly presented, and apparently was not related to a concomitant high dose of steroids or malnutrition in the patients. It seems that in addition to the already well known autoimmune abnormalities that occur in MCTD, there are other features like the presence of lymphadenopathy, the high polyclonal increase of gammaglobulins, and the lymphopenia, that reflect the profound disturbance of the immune system in this syndrome, possibly contributing to the sudden appearance of a severe infectious disease in some of our patients.

HLA type as a predictor of mixed connective tissue disease differentiation. Ten-year clinical and immunogenetic followup of 46 patients.

OBJECTIVE: To determine any clinical or genetic markers of differentiation and outcome in a previously described cohort of 46 patients with mixed connective tissue disease (MCTD). METHODS: Patients were clinically evaluated, chart notes reviewed, and HLA subtyping and immunology profiles performed where possible. Eleven had died and 7 were lost to followup. RESULTS: MCTD had differentiated into systemic lupus erythematosus in 12 patients and into systemic sclerosis in 13. The latter was associated with HLA-DR5 (P = 0.038), and nondifferentiation was associated with HLA-DR2 or DR4 (P = 0.007). Three HLA-DR4 positive patients had MCTD that evolved into rheumatoid arthritis. Erosive and/or deforming arthritis was associated with HLA-DR1 or DR4 (P = 0.015). HLA-DR3 was associated with interstitial lung fibrosis (P = 0.044) and keratoconjunctivitis sicca (0.001 < P < 0.01). Severe Raynaud's phenomenon predicted higher mortality (0.01 < P < 0.05). CONCLUSION: We suggest that MCTD is, for most patients, an intermediate stage in a genetically determined progression to a recognized connective tissue disease. Those whose disease remains undifferentiated might be considered a distinct subset.

Pneumatosis intestinalis and pneumoperitoneum complicating mixed connective tissue disease.

A case of a young woman with a 3-year history of mixed connective tissue disease who developed secondary pneumatosis intestinalis and pneumoperitoneum and died shortly after of rapidly progressive disease is reported. The pathogenesis, treatment and prognosis of this unusual complication in mixed connective tissue disease are discussed.

[Fatal pulmonary hypertension in Sharp syndrome (M.C.T.D.) with pulmonary fibrosis]. / Hypertension pulmonaire fatale dans un syndrome de Sharp (M.C.T.D.) avec fibrose pulmonaire.

We have followed a case of Mixed Connective Tissue Disease (M.C.T.D.) during 5 years. A progressive pulmonary hypertension inducing cor pulmonary failure terminated in a fatal issue. The prognosis of M.C.T.D. previously considered good is sometimes more severe in spite of immunosuppressive therapy.