OBJECTIVE: Pulmonary hypertension (PH) develops frequently in connective tissue diseases (CTD) and is an important prognostic factor. The aim of this study was to assess the prevalence of PH in patients with CTD by non-invasive echocardiography and analyze the potential biomarkers for helping to detect PH. METHODS: All Korean patients with CTD who had dyspnea on exertion or interstitial lung disease (ILD) were screened for PH with echocardiography and clinical data were collected from four hospitals. RESULTS: Among 196 patients with CTD, 108 (55.1%) had ILD and 21 had PH defined as >40 mmHg. Of the 21 patients with PH, 10, 4, and 3 patients had systemic sclerosis, systemic lupus erythematosus, and mixed connective tissue disease, respectively. There was no difference in the incidence of PH according to the presence of ILD; 12 patients (11.1%) with ILD had PH and 9 patients (10.2%) without ILD had PH. The results of the pulmonary function test, total cholesterol, red cell volume distribution width, alkaline phosphatase, and the New York Heart Association (NYHA) functional class III or IV differed significantly according to the presence of PH. In multiple regression analysis, NYHA functional class III or IV (odd ratio [OR]=7.3, p=0.009) and forced vital capacity (OR=0.97, p=0.043) were independent predictive factors of PH. CONCLUSION: PH is not associated with the presence of ILD in Korean patients with CTD. On the other hand, NYHA functional class III or IV and decreased forced vital capacity indicate the presence of PH in connective tissue disease.
Alkaline Phosphatase ; Biomarkers ; Cell Size ; Cholesterol ; Connective Tissue Diseases* ; Connective Tissue* ; Dyspnea ; Echocardiography ; Hand ; Heart* ; Humans ; Hydrogen-Ion Concentration ; Hypertension, Pulmonary* ; Incidence ; Lung Diseases, Interstitial* ; Lupus Erythematosus, Systemic ; Mixed Connective Tissue Disease ; Prevalence ; Respiratory Function Tests ; Risk Factors ; Scleroderma, Systemic ; Vital Capacity*

A 40-year-old female previously diagnosed with primary biliary cirrhosis was referred to the hospital complaining of muscle weakness, arthralgia, Raynaud's phenomenon, and thick skin. After work-up, she was diagnosed with both mixed connective tissue disease (MCTD) and papillary thyroid cancer (PTC), based on the Alarcon-Segovia criteria and pathological examination, respectively. High-dose glucocorticoid and azathioprine were introduced to treat active myositis of MCTD, and total thyroidectomy was performed to treat PTC. This report highlights the possible association between MCTD and thyroid cancer, and suggests that MCTD is associated with PTC, similar to other autoimmune diseases including Sjögren's syndrome, systemic sclerosis, and systemic lupus erythematosus.
Adult ; Arthralgia ; Autoimmune Diseases ; Azathioprine ; Female ; Humans ; Liver Cirrhosis, Biliary* ; Lupus Erythematosus, Systemic ; Mixed Connective Tissue Disease* ; Muscle Weakness ; Myositis ; Scleroderma, Systemic ; Skin ; Thyroid Gland* ; Thyroid Neoplasms* ; Thyroidectomy

Nailfold capillaroscopy (NFC) is a non-invasive morphological study that routinely used to differentiate between a primary and secondary Raynaud's phenomenon (RP). Secondary RP is a manifestation of an underlying rheumatic disease that occurs in 80-95% of patients with systemic sclerosis (SSc), 75% of patients with mixed connective tissue disease and in 20-25% of patients with systemic lupus erythematosus or rheumatoid arthritis. These RP frequently precedes the underlying disease by many years. The well-established roles of NFC are the early diagnosis of SSc, and potential for predicting clinical complication, as like digital ulcers. The following review will present a technique about how to perform NFC and optimal assessment with emphasis on its possible role as a reliable diagnostic tool.
Arthritis, Rheumatoid ; Early Diagnosis ; Humans ; Lupus Erythematosus, Systemic ; Microscopic Angioscopy* ; Mixed Connective Tissue Disease ; Rheumatic Diseases* ; Scleroderma, Systemic ; Treatment Outcome* ; Ulcer

Incidence of renal involvement in mixed connective tissue disease (MCTD) is low. In the presence of glomerulonephritis, membranous nephropathy (MN) in MCTD is common. A 47-year-old woman presented with hypothyroidism. She developed Raynaud's phenomenon, arthralgia, and incomplete lupus erythematosus, diagnosed with MCTD. One year after then, the patient developed persistent proteinuria (1+) without hematuria. Following diagnosis with MCTD, her renal function began to deteriorate. The renal biopsy showed late stage MN. For the treatment of MN with mild proteinuria and MCTD, we prescribed an angiotensin II receptor blocker and 7.5 mg of methotrexate per week and 300 mg of hydroxychloroquine daily. The patient had a reduced estimated glomerular filtration rate of 55% for the subsequent eight years. The MN in MCTD is known to show good renal prognosis. Here, we report on a rare case of MN in MCTD in Korea with a bad prognosis.
Arthralgia ; Biopsy ; Diagnosis ; Female ; Glomerular Filtration Rate ; Glomerulonephritis ; Glomerulonephritis, Membranous* ; Hematuria ; Humans ; Hydroxychloroquine ; Hypothyroidism ; Incidence ; Korea ; Methotrexate ; Middle Aged ; Mixed Connective Tissue Disease* ; Prognosis* ; Proteinuria ; Receptors, Angiotensin

BACKGROUND: Mixed connective tissue disease (MCTD) is a distinct autoimmune disease with overlapping features of different connective tissue diseases and a broad spectrum of presentation and prognosis. Our aim is to present the clinical profile of a cohort of Filipinos with MCTD.
METHODS: Charts with diagnosis of MCTD based on the Alarcon-Segovia Criteria from the Philippine General Hospital Adult Rheumatology clinic from January 1999 to December 2011 were reviewed for demographics, clinical presentation, and management. Descriptive statistics were applied.
RESULTS: Fourteen patients were identified to have MCTD. All were females. The median age at symptom onset, and at diagnosis, was 30.5, and 31.5 years, respectively, with two having juvenile onset of symptoms. Mean interval from symptom onset to diagnosis is two years. Patients are being followed up for the past mean of 3.5 years.All eight women    who wanted children were able to conceive, and among them only two had fetal losses but were negative for antiphospholipid antibodies. Chief complaint was most commonly joint pain (67%) followed by skin tightness (13%). Systemic lupus erythematosus (SLE) was the most frequent initial diagnosis (43%). Majority had initial constitutional symptoms with generalized weakness and fatigue being the most frequent (93%). Most common physical findings in different body systems are as follows: musculoskeletal - arthritis (100%); vascular - Raynaud's phenomenon (93%); cutaneous- skin tightness (71%); gastrointestinal - dental caries (57%); hematologic - anemia of chronic disease (50%); cardiopulmonary - accentuated pulmonary component of the second heart sound and right ventricular hypertrophy (21% each); neurologic - peripheral neuropathy (21%); renal - proteinuria (21%); endocrine - autoimmune thyroiditis (21%).Half have anemia of chronic disease. Only three (21%) have proteinuria and were below nephrotic range. Twelve out of 12 have elevated sedimentation rates. For serologic studies, all have speckled ANA  and very  high  titers  of  anti-U1RNP;six of six patients have  normal  rheumatoid  factor(RF) titers; one    out    of  two  have  positive  anti-Ro;two out of four have anti-Ds DNA; none of two have anti-SCL70.Majority of the chest x-rays,electrocardiograms,echocardiographs  were  normal.Three have pulmonary hypertension. One out of four has restrictive lung disease on pulmonary function test. Most are in remission and are on low-dose prednisone (79%), hydroxychloroquine (50%), nifedipine (36%) and methotrexate (21%).
CONCLUSION: This is the first study that detailed clinical and laboratory features of Filipinos with MCTD diagnosed using the Alarcon-Segovia criteria. Most clinical features, disease activity, and management are concordant with international data. Possible peculiarities include fewer interstitial lung disease, esophageal dysmotility, thrombocytopenia and leucopenia, and RF titers. We intend to add newly diagnosed patients and pursue this cohort for us to better understand the course of MCTD in Filipinos that could translate to better patient care.

Human ; Female ; Adult ; Mixed Connective Tissue Disease ; Hydroxychloroquine ; Hypertrophy, Right Ventricular ; Thyroiditis, Autoimmune ; Lupus Erythematosus, Systemic ; Antibodies, Antiphospholipid ; Raynaud Disease ; ;

OBJECTIVE: To investigate the diagnosis and treatment of mixed connective tissue disease (MCTD) and myeloperoxidase-antineutrophil cytoplasmic antibody (MPO-ANCA) associated vasculitis, which is a rare clinical entity in medical practice. METHODS: A 35-year-old female of Asian origin was admitted to our hospital due to complaints of Raynaud's phenomenon, myalgia, arthralgia and fatigue. The patient was diagnosed as MCTD in the out-patient department 8 months prior to admission based on Alarcon-Segovia classification criteria of Raynaud's phenomenon, myalgia, arthralgia and a high anti-U1 ribonucleoprotein antibody level. Interstitial lung disease was determined by chest computed tomography. Renal biopsy was performed because of marked proteinuria on 24 h urine collection. Histopathological examination revealed glomerulonephritis with fibrocellular/cellular crescents, in which moderate staining of IgM was shown by direct immunofluorescence. She was tested positive for myeloperoxidase antineutrophil cytoplasmic antibody. RESULTS: High dose of methylprednisolone (500 mg/d for 3 days) was started intravenously when the results of renal biopsy were obtained. Oral prednisone and intravenous cyclophosphamide therapy (0.8 g/month) were continued for 12 months. Daily urinary protein loss decreased dramatically and serum creatinine was maintained at a normal level. CONCLUSION Corticosteroids and cyclophosphamide are effective in the treatment of MPO-ANCA associated glomerulonephritis in MCTD.
Adult ; Antibodies, Antineutrophil Cytoplasmic ; Cyclophosphamide ; Female ; Glomerulonephritis ; Humans ; Methylprednisolone ; Mixed Connective Tissue Disease ; Peroxidase ; Proteinuria

Mixed connective tissue disease (MCTD) was first described by Sharp and coworkers in 1972, characterized by symptoms of Raynaud's phenomenon or swollen hands, overlapping clinical features of systemic lupus erythematosus, systemic sclerosis, or polymyositis/dermatomyositis, and the presence of anti-U1 RNP antibody. MCTD is rare in children and constitutes 0.3~0.6% of all rheumatologic patients in pediatric rheumatology database of the United States. Here, we report the first Korean case of a 10-year-old female patient with MCTD, presenting Raynaud's phenomenon in the hands, feet, and tongue.
Child ; Female ; Foot ; Hand ; Humans ; Lupus Erythematosus, Systemic ; Mixed Connective Tissue Disease ; Rheumatology ; Scleroderma, Systemic ; Tongue ; United States

Barrett's esophagus is a metaplasia of the esophageal epithelium of any length, such that normal squamous epithelium is replaced by specialized columnar epithelium with goblet cells. It is important to diagnose and survey Barrett's esophagus because it is believed to be the major risk factor for development of esophageal adenocarcinoma. However, the prevalence of Barrett's esophagus in Korea is low. Mixed connective tissue disease (MCTD) is a systemic disorder in which patients have combinations of the clinical features of systemic lupus erythematosus, systemic sclerosis, and polymyositis. Although gastroesophageal reflux disease is common in esophageal involvement in MCTD, long-segment Barrett's esophagus in MCTD has not been reported in Korea. We report here a 15 cm-long segment of Barrett's esophagus extending to the proximal esophagus in a female patient who has had MCTD for 2 years, and we review the literature.
Adenocarcinoma ; Barrett Esophagus ; Epithelium ; Esophagus ; Female ; Gastroesophageal Reflux ; Goblet Cells ; Humans ; Korea ; Lupus Erythematosus, Systemic ; Metaplasia ; Mixed Connective Tissue Disease ; Polymyositis ; Prevalence ; Risk Factors ; Scleroderma, Systemic

Barrett's esophagus is a metaplasia of the esophageal epithelium of any length, such that normal squamous epithelium is replaced by specialized columnar epithelium with goblet cells. It is important to diagnose and survey Barrett's esophagus because it is believed to be the major risk factor for development of esophageal adenocarcinoma. However, the prevalence of Barrett's esophagus in Korea is low. Mixed connective tissue disease (MCTD) is a systemic disorder in which patients have combinations of the clinical features of systemic lupus erythematosus, systemic sclerosis, and polymyositis. Although gastroesophageal reflux disease is common in esophageal involvement in MCTD, long-segment Barrett's esophagus in MCTD has not been reported in Korea. We report here a 15 cm-long segment of Barrett's esophagus extending to the proximal esophagus in a female patient who has had MCTD for 2 years, and we review the literature.
Adenocarcinoma ; Barrett Esophagus ; Epithelium ; Esophagus ; Female ; Gastroesophageal Reflux ; Goblet Cells ; Humans ; Korea ; Lupus Erythematosus, Systemic ; Metaplasia ; Mixed Connective Tissue Disease ; Polymyositis ; Prevalence ; Risk Factors ; Scleroderma, Systemic

Mixed connective tissue disease (MCTD) has the clinical feature of other collagen vascular diseases. According to several reports recently published, MCTD sometimes involved kidney as benign course. ANCA associated glomerulonephritis occurred in systemic autoimmune disease such as systemic sclerosis or rheumatoid arthritis, not in MCTD. In this case, as we experienced that MPO-ANCA associated glomerulonephritis arose and proceeded to rapid progressive glomerulonephritis (RPGN) in women with MCTD, we report it with review of reference. A 60-year-old woman was admitted with uremia and joint pain. In physical finding and serum test, she was diagnosed with MCTD according to Khan`s criteria. Also MPO antibody and ANCA were noted in specific immunological test and the histologic findings showed crescentic glomerulonephritis. So we diagnosed RPGN induced by MPO-ANCA associated glomerulonephritis. She was treated with immunosuppressive treatment and uremia was improved. RPGN induced by MPO-ANCA associated glomerulonephritis should be ruled out by prompt renal biopsy and require proper treatment.
Antibodies, Antineutrophil Cytoplasmic ; Arthralgia ; Arthritis, Rheumatoid ; Autoimmune Diseases ; Biopsy ; Collagen ; Female ; Glomerulonephritis ; Humans ; Immunologic Tests ; Kidney ; Middle Aged ; Mixed Connective Tissue Disease ; Scleroderma, Systemic ; Uremia ; Vascular Diseases