Due to its low prevalence and because there is lack of awareness about it, Loeys-Dietz syndrome is often mis-diagnosed as Marfan syndrome, which has similar skeletal abnormalities and aortic pathology. However, the differential diagnosis between these two connective tissue diseases is critical because they correspond to different surgical indications and surgical decision-making. We report two cases of successful thoracoabdominal aortic replacement in patients with previously undiagnosed Loeys-Dietz syndrome.
Aortic Aneurysm ; Connective Tissue Diseases ; Diagnosis, Differential ; Humans ; Loeys-Dietz Syndrome* ; Marfan Syndrome ; Pathology ; Prevalence

BACKGROUNDStevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are life-threatening diseases with high mortality rates. This study was designed to analyze the pathogenic factors, clinical manifestations, complications, treatment, and prognosis of SJS/TEN and to explore the differences between surviving and deceased patients.

METHODSSJS/TEN patients admitted to Beijing Friendship Hospital from January 2006 to December 2015 were included in the study. Patients' data were retrospectively analyzed. Comparative studies were performed on the survival group and the deceased group, and Fisher's exact probability test was used for statistical analysis.

RESULTSAmong the 88 patients included, 40 (45.5%) were male with a mean age of 45 ± 18 years. Forty-eight (54.5%) had SJS, 34 (38.6%) had SJS/TEN, and 6 (6.8%) had TEN. Fifty-three (60.2%) cases were caused by medications, mainly antibiotics (n = 24) followed by traditional Chinese medicines (n = 7). Forty-two cases (47.7%) developed visceral damage. Eighty-two patients improved or recovered and were discharged from hospital, and six patients died. Comparative studies on the survival group and the deceased group showed that the presence of malignant tumor ( χ2 = 27.969,P < 0.001), connective tissue diseases ( χ2 = 9.187, P= 0.002), previous abnormal liver/kidney functions ( χ2 = 6.006, P= 0.014), heart rate >100 times/min ( χ2 = 6.347, P= 0.012), detached skin area >20% ( χ2 = 5.594, P= 0.018), concurrent mucosal involvement at the mouth, eyes, and external genitals ( χ2 = 4.945, P= 0.026), subsequent accompanying liver/kidney damage ( χ2 = 11.839, P= 0.001, and χ2 = 36.302,P < 0.001, respectively), and SCORTEN score >2 ( χ2 = 37.148,P < 0.001) increased the risk of death.

CONCLUSIONSSJS/TEN is mainly caused by medications, and nearly half of patients develop visceral damage. Multiple factors increase the mortality risk.

Adult ; Anti-Bacterial Agents ; therapeutic use ; Connective Tissue Diseases ; metabolism ; pathology ; Eye ; pathology ; Female ; Genitalia ; pathology ; Humans ; Kidney ; metabolism ; pathology ; Liver ; metabolism ; pathology ; Male ; Middle Aged ; Mouth ; pathology ; Retrospective Studies ; Skin ; metabolism ; pathology ; Stevens-Johnson Syndrome ; drug therapy ; metabolism ; pathology

OBJECTIVETo investigate the prevalence of anti-endothelial cell antibodies (AECAs) in the sera of connective tissue diseases (CTD) patients with pulmonary arterial hypertension (PAH) and its correlation with clinical manifestations.

METHODSAECAs in sera of 39 CTD patients with PAH, 22 CTD patients without PAH, and 10 healthy donors as controls were detected with Western blotting. The prevalence of different AECAs in different groups was compared and its correlation with clinical manifestations was also investigated.

RESULTSThe prevalence of AECAs was 82.1% in CTD patients with PAH, 72.7% in CTD patients without PAH, and 20.0% in healthy donors. Anti-22 kD AECA was only detected in CTD patients with PAH (15.4%). Anti-75 kD AECA was more frequently detected in CTD patients with PAH than in those without PAH (51.3% vs. 22.7%, P < 0.05). In CTD patients with PAH, anti-75 kD AECA was more frequently detected in those with Raynaud's phenomenon or with positive anti-RNP antibody.

CONCLUSIONAECAs could be frequently detected in CTD patients with or without PAH, while anti-22 kD and anti-75 kD AECA might be specific in CTD patients with PAH.

Adult ; Autoantibodies ; blood ; immunology ; Cell Line ; Connective Tissue Diseases ; blood ; immunology ; pathology ; physiopathology ; Endothelial Cells ; cytology ; immunology ; Female ; Humans ; Hypertension, Pulmonary ; blood ; immunology ; pathology ; physiopathology ; Middle Aged

Inflammation from chronic and acute infections of distal organs and tissues such as periodontitis is a risk factor for atherosclerotic vascular processes. Recently, a new model of atherosclerosis with vascular pathologies was developed in the Mongolian gerbil. In this study, we attempted to develop a model of ligature-induced periodontitis in gerbils and compared the characteristics of that periodontitis model with that in rats and mice. Each gerbil, rat, and mouse was randomly assigned to groups of control and periodontitis. A thread was placed around the cervix of the right and left first molars in the mandible with knots placed on the mesial side of each molar. At day 14 after the ligation, the animals were sacrificed and their mandibles were dissected. To measure alveolar bone loss along with inflammation, histopathological and micro-CT analyses were carried out. Gerbils showed tooth characteristics of deeper gingival crevice, longer cusp, longer root trunk and shorter root than those of rats and mice. The increased CEJ-ABC distance in distal and PDL area in furcation was also observed in ligated gerbils. An inflammatory response in the connective tissue under the junctional epithelium was also shown in all the animals. As a result, we confirmed the induction of periodontitis by ligature in the gerbils. We therefore consider the gerbil to be a useful model for investigating relationship between periodontitis and vascular disease in the same animal.
Alveolar Bone Loss ; Animals* ; Atherosclerosis ; Cervix Uteri ; Connective Tissue ; Epithelial Attachment ; Female ; Gerbillinae* ; Inflammation ; Ligation ; Mandible ; Mice ; Models, Animal* ; Molar ; Pathology ; Periodontitis* ; Rats ; Risk Factors ; Tooth ; Vascular Diseases

Animals ; Arginine Vasopressin ; physiology ; Connective Tissue Growth Factor ; physiology ; Glomerular Mesangium ; pathology ; Humans ; Integrin alpha1beta1 ; physiology ; Kidney Diseases ; etiology ; Proto-Oncogene Protein c-ets-1 ; physiology

Although autoantibodies are routinely screened in patients with idiopathic interstitial pneumonia, there are no reliable data on their clinical usefulness. The aim of this study was to investigate the prognostic value of autoantibodies for predicting the development of new connective tissue disease in these patients and also mortality. We conducted retrospective analysis of the baseline, and follow-up data for 688 patients with idiopathic interstitial pneumonia (526 with idiopathic pulmonary fibrosis, 85 with nonspecific interstitial pneumonia, and 77 with cryptogenic organizing pneumonia) at one single tertiary referral center. The median follow-up period was 33.6 months. Antinuclear antibody was positive in 34.5% of all subjects, rheumatoid factor in 13.2%, and other specific autoantibodies were positive between 0.7%-6.8% of the cases. No significant difference in patient survival was found between the autoantibody-positive and -negative groups. However, the presence of autoantibodies, especially antinuclear antibody with a titer higher than 1:320, was a significant predictor for the future development of new connective tissue diseases (relative risk, 6.4), although the incidence was low (3.8% of all subjects during follow-up). In conclusion, autoantibodies are significant predictors for new connective tissue disease development, although they have no prognostic value.
Aged ; Antibodies, Antinuclear/blood ; Autoantibodies/*blood ; Cohort Studies ; Connective Tissue Diseases/pathology ; Female ; Follow-Up Studies ; Humans ; Idiopathic Interstitial Pneumonias/*blood/diagnosis ; Male ; Middle Aged ; Prognosis ; Retrospective Studies ; Rheumatoid Factor/blood ; Risk Factors ; Tertiary Care Centers ; Tomography, X-Ray Computed

Two major vascular pathologies underlie brain damage in patients with disease of small size penetrating brain arteries and arterioles; 1) thickening of the arterial media and 2) obstruction of the origins of penetrating arteries by parent artery intimal plaques. The media of these small vessels may be thickened by fibrinoid deposition and hypertrophy of smooth muscle and other connective tissue elements that accompanies degenerative changes in patients with hypertension and or diabetes or can contain foreign deposits as in amyloid angiopathy and genetically mediated conditions such as cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. These pathological changes lead to 2 different pathophysiologies: 1) brain ischemia in regions supplied by the affected arteries. The resultant lesions are deep small infarcts, most often involving the basal ganglia, pons, thalami and cerebral white matter. And 2) leakage of fluid causing edema and later gliosis in white matter tracts. The changes in the media and adventitia effect metalloproteinases and other substances within the matrix of the vessels and lead to abnormal blood/brain barriers in these small vessels. and chronic gliosis and atrophy of cerebral white matter.
Adventitia ; Amyloid ; Arteries ; Arterioles ; Atrophy ; Basal Ganglia ; Brain ; Brain Ischemia ; CADASIL ; Cerebral Amyloid Angiopathy ; Cerebral Small Vessel Diseases ; Connective Tissue ; Edema ; Gliosis ; Humans ; Hypertension ; Hypertrophy ; Metalloproteases ; Muscle, Smooth ; Parents ; Pathology* ; Pons ; Stroke, Lacunar* ; Tunica Media

Collagen is the major structural protein in the human body, especially in connective tissues. There are more than 13 types of collagen. Among them, type II collagen is a main component of articular cartilage structure. Altered immunological conditions against type II collagen may be closely related to the pathologic conditions of joint, especially arthritis. Since 1977, animal model for collageninduced arthritis(CIA) has been developed and used in the investigation of arthritis. In those animals, high titers of anti-type II collagen antibody were noticed. Pathologic findings were similar to rheumatoid arthritis of human, which suggested that rheumatoid arthritis might be one of the autoimmune diseases. There had been many reports about elevation of serum and synovial level of anti-type II collagen antibody in rheumatoid arthritis patients. But majority of them did not discriminate the antibody titers according to the type of immunoglobulin(i.e. IgG, IgM). And the question whether the elevated antibody titers are cause or effect of the arthritis is still in controversy. In this study, the serum levels of anti-type II collagen antibody were determined in 82 persons(35 degenerative arthritis patients, 24 rheumatoid arthritis patients and 22 normal controls without any joint problem) via ELISA method. In each person the serum IgG, IgM and IgG+M+A antibody levels against bovine type IIcollagen and chicken typeII collagen were determined individually. Statistical evaluation of these data among degenerative arthritis group, rheumatoid arthritis group and normal control group was performed. The results were as follows; 1. Degenerative arthritis group revealed significant elevation of anti-type II collagen antibody(IgG, IgG+M+A) compared to normal control(p < 0.05). 2. Rheumatoid arthritis group showed significant elvation of IgM and IgG+M+A compared to normal control. 3. Between degenerative arthritis and rheumatoid arthritis group, no sigificant difference was noticed. 4. Rheumatoid arthritis group showed significant increase of IgM antibody level compared to normal control. 5. Female rheumatoid arthritis group showed significant increase of IgM level compared to female degenerative arthritis group. These findings suggested that the elevation of anti-type II collagen antibody titer is not specific for rheumatoid arthritis and related with general pathologies destroying articular cartilage. And it is suggested that anti-type II collagen antibody associated with rheumatoid arthritis is mainly IgM proportion, especially in female patients. So further investigation of anti-type II collagen antibody associated with rheumatoid arthritis is needed to target IgM antibody.
Animals ; Arthritis ; Arthritis, Rheumatoid ; Autoimmune Diseases ; Cartilage, Articular ; Chickens ; Collagen ; Collagen Type II ; Connective Tissue ; Enzyme-Linked Immunosorbent Assay ; Female ; Human Body ; Humans ; Immunoglobulin G ; Immunoglobulin M ; Joints ; Methods ; Models, Animal ; Osteoarthritis ; Pathology

Stickler syndrome is a genetically heterogeneous disorder that affects the ocular, auditory, and musculoskeletal systems. Ocular-only variant of Stickler syndrome type 1 (OSTL1) is characterized by high risk of retinal detachment without systemic involvement and is caused by alternatively spliced exon 2 mutation of COL2A1. We report the cases of two Korean families with OSTL1 carrying likely pathogenic variants of COL2A1. All patients presented with membranous vitreous anomaly, peripheral retinal degeneration, and/or rhegmatogenous retinal detachment, but no systemic manifestations. By genetic analysis, two likely pathogenic non-exon 2 variants, c.2678dupC (p.Ala895Serfs*49) and c.3327+ 1G>C, were identified in COL2A1. Our results demonstrate that COL2A1 defects in OSTL1 are not confined to mutations in exon 2. Together with molecular data, ophthalmologists should consider genetic diagnosis of Stickler syndrome in patients with vitreous anomaly to prevent blindness from retinal detachment. To our knowledge, this is the first report of genetically confirmed OSTL1 in Korea.
Adult ; Arthritis/*genetics/pathology ; Asian Continental Ancestry Group/*genetics ; Base Sequence ; Collagen Type II/*genetics ; Connective Tissue Diseases/*genetics/pathology ; DNA Mutational Analysis ; Exons ; Female ; Hearing Loss, Sensorineural/*genetics/pathology ; Humans ; Male ; Middle Aged ; Republic of Korea ; Retinal Detachment/*genetics/pathology ; Visual Acuity

OBJECTIVETo study the effects of astaxanthin on renal fibrosis and apoptosis induced by partial unilateral ureteral obstruction (UUO) in rats.

METHODSNinety-six male adult SD rats were randomized into 6 equal groups, namely the blank control group, sham-operated group, UUO group, and astaxanthin group at high, medium, and low doses. Left ureteral ligation was performed in UUO and astaxanthin groups, and two days before the operation, the rats in astaxanthin groups were lavaged with 25, 50, or 100 mg/kg astaxanthin daily for 14 days, while the same volume of saline was given to rats in UUO group and sham-operated group. Renal pathological in the rats was observed with HE staining, and the expression levels of TGF-β1, SGK1, and CTGF in the left kidney were detected immunohistochemically; the expression level of Bcl-2 and Bax were detected using Bcl-2 and Bax detection kits.

RESULTSCompared to UUO group, high- and medium-dose astaxanthin groups showed obviously ameliorated renal pathologies and reduced expressions of TGF-β1, SGK1, and CTGF in the left kidney with lessened renal cell apoptosis.

CONCLUSIONAstaxanthin can reduce UUO-induced renal fibrosis and renal cell apoptosis, demonstrating the renoprotective effect of astaxanthin against renal fibrosis.

Animals ; Apoptosis ; drug effects ; Connective Tissue Growth Factor ; metabolism ; Fibrosis ; Immediate-Early Proteins ; metabolism ; Kidney ; drug effects ; metabolism ; pathology ; Kidney Diseases ; metabolism ; pathology ; Male ; Protein-Serine-Threonine Kinases ; metabolism ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; Rats ; Rats, Sprague-Dawley ; Transforming Growth Factor beta1 ; metabolism ; Ureteral Obstruction ; metabolism ; pathology ; Xanthophylls ; pharmacology ; bcl-2-Associated X Protein ; metabolism