Hsien Tzung Liao

Factors associated with radiographic spinal involvement and hip involvement in ankylosing spondylitis.

OBJECTIVES To determine the factors associated with radiographic spinal involvement and hip involvement in ankylosing spondylitis (AS) and assess the influence of the damage seen in the radiographs on functional outcome in patients with AS. METHODS We included 531 consecutive patients and recorded the clinical, laboratory, and radiographic data. Based on the spinal radiographs, patients were classified into 3 categories: (1) no spinal involvement; (2) spinal involvement without fusion; and (3) spinal involvement with fusion. Hip involvement was assessed by the Bath Ankylosing Spondylitis Radiology Hip Index and defined by a score of at least 2. Logistic regression analyses were used to investigate the factors associated with the radiographic spine and hip involvements. RESULTS Ninety-eight (18.5%) patients had radiographic evidence of spinal fusion and 48 (9.0%) had radiographic evidence of hip involvement. Patients who had longer disease duration, elevated C-reactive protein levels, advanced sacroiliitis, and radiographic hip involvement were significantly more likely to have spinal fusion (P < 0.05). Elevated C-reactive protein levels and advanced sacroiliitis were also significantly associated with the presence of spinal involvement without fusion (P < 0.05). Early disease onset and more radiographic severity in the spine and sacroiliac joints were the predictors of radiographic hip involvement (P < 0.05). Patients with either spine or hip involvement had significantly higher Bath Ankylosing Spondylitis Functional Index scores (P < 0.001). CONCLUSION There is a relationship between radiographic sacroiliitis, spinal fusion, and hip involvement in patients with AS. Damage to the spine and hip seen radiographically can contribute to functional impairment.

Association of acute anterior uveitis with disease activity, functional ability and physical mobility in patients with ankylosing spondylitis: a cross-sectional study of Chinese patients in Taiwan

Acute anterior uveitis (AAU) is the most frequently extra-articular manifestation of ankylosing spondylitis (AS). To investigate whether AAU has an association with disease activity, functional ability and physical mobility in AS patients, 146 Chinese AS patients in Taiwan were enrolled in a cross-sectional study. These patients fulfilled the 1984 modified New York criteria and visited the Outpatient Department of the Veterans General Hospital-Taipei from April 2004 to July 2005. Patients completed questionnaires assessing disease activity [Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)], functional ability [Bath Ankylosing Spondylitis Functional Index (BASFI)] and patient’s global assessment [Bath Ankylosing Spondylitis Patient Global Score (BAS-G)]. Meanwhile, physical examinations were performed, including Schober test, finger-to-floor, lateral spinal flexion, occiput-to-wall and chest expansion. The history of AAU was accepted only if diagnosed by an ophthalmologist. The prevalence of AAU in this Chinese AS cohort was 15.8% (23/146). Patients with AAU had a significantly higher BASDAI than those without [absolute differences=0.96, 95% confidence intervals (CI): 0.35∼1.88]. Additionally, patients with AAU had significantly increased BASFI than those without (absolute differences=1.46, 95% CI: 0.33∼2.59). Moreover, there was advanced limitation of physical motility in patients with AAU, including finger-to-floor, occiput-to-wall distances and Schober test, (95% CI: 3.89∼16.95 and p=0.046, respectively). Disease duration mildly correlated with BASFI (r=0.24, p=0.003) but not with BASDAI (p=0.838). There was no difference of disease duration between patients with and without AAU (p=0.343). These results suggested that the presence of AAU in AS patients may be associated with higher disease activity, poor functional ability and advanced physical impairment.

Clinical, Functional, and Radiographic Differences Among Juvenile-onset, Adult-onset, and Late-onset Ankylosing Spondylitis

Objective. The aim of our study was to compare the clinical, functional, and radiographic outcomes at different ages of onset in patients with ankylosing spondylitis (AS). Methods. A total of 546 patients were enrolled consecutively and classified into 3 groups based on their age at symptom onset: (1) juvenile-onset AS (age ≤ 16 years; JoAS); (2) adult-onset AS (> 16 but < 40 years; AoAS); and (3) late-onset AS (≥ 40 years; LoAS). We compared the differences among the 3 groups. OR for disease outcomes were calculated and adjusted for sex, HLA-B27, and disease duration. Results. There were 67 patients (12.3%) with JoAS, 460 (84.2%) with AoAS, and 19 (3.5%) with LoAS. Male sex and HLA-B27 were associated with a younger age at onset (p < 0.001). Compared to patients with AoAS, patients with JoAS were more likely to present with peripheral arthritis, while patients with JoAS and LoAS were less likely to have back pain at the onset of AS (p < 0.05). After controlling for multiple covariates, JoAS was found to be associated with a worse functional outcome and global assessment, and a high serum immunoglobulin A level (p < 0.05). Patients with JoAS had less lumbar spinal radiographic severity (p < 0.05). There were no statistical differences in clinical or functional outcome between the LoAS and AoAS groups. None of the LoAS patients had radiographic hip involvement. Conclusion. Sex and HLA-B27 are significantly associated with age at onset of AS. Both JoAS and LoAS have their distinctive symptoms/signs at onset and different disease outcomes.

Leukocyte Mitochondrial DNA Alteration in Systemic Lupus Erythematosus and Its Relevance to the Susceptibility to Lupus Nephritis

The role of mitochondrial DNA (mtDNA) alterations in the pathophysiology of systemic lupus erythematosus (SLE) remains unclear. We investigated sequence variations in the D310 region and copy number change of mtDNA in 85 SLE patients and 45 normal subjects. Leukocyte DNA and RNA were extracted from leukocytes of the peripheral venous blood. The D310 sequence variations and copy number of mtDNA, and mRNA expression levels of mtDNA-encoded genes in leukocytes were determined by quantitative real-time polymerase chain reaction (Q-PCR) and PCR-based direct sequencing, respectively. We found that leukocyte mtDNA in SLE patients exhibited higher frequency of D310 heteroplasmy (69.4% vs. 48.9%, p = 0.022) and more D310 variants (2.2 vs. 1.7, p = 0.014) than those found in controls. Among normal controls and patients with low, medium or high SLE disease activity index (SLEDAI), an ever-increasing frequency of D310 heteroplasmy was observed (p = 0.021). Leukocyte mtDNA copy number tended to be low in patients of high SLEDAI group (p = 0.068), especially in those harboring mtDNA with D310 heteroplasmy (p = 0.020). Moreover, the mtDNA copy number was positively correlated with the mRNA level of mtDNA-encoded ND1 (NADH dehydrogenase subunit 1) (p = 0.041) and ATPase 6 (ATP synthase subunit 6) (p = 0.030) genes. Patients with more D310 variants were more susceptible to lupus nephritis (p = 0.035). Taken together, our findings suggest that decrease in the mtDNA copy number and increase in D310 heteroplasmy of mtDNA are related to the development and progression of SLE, and that the patients harboring more D310 variants of mtDNA are more susceptible to lupus nephritis.

Association of cigarette smoking with Chinese ankylosing spondylitis patients in Taiwan: A poor disease outcome in systemic inflammation, functional ability, and physical mobility

We investigated the association between smoking and the disease activity, functional ability, physical mobility, and systemic inflammation in Chinese ankylosing spondylitis (AS) patients. Seventy five male Chinese AS patients in Taiwan were enrolled in the cross-sectional study. These patients fulfilled the 1984 modified New York criteria. Patients completed the questionnaires, containing the demographic data, disease activity, functional ability (BASFI), and patient’s global assessment. Meanwhile, physical examinations were performed to determine the patient’s physical mobility. Acute-phase reactants, erythrocyte sedimentation rate (ESR), and C-reactive protein levels were also measured in the AS patients. Smoking habits with smoking duration and smoking intensity (pack–years of smoking) were recorded. Among these physical mobility parameters, modified Schober’s index (p < 0.001), cervical rotation (p = 0.034), later lumbar flexion (p = 0.002), chest expansion (p = 0.016), and occiput-to-wall distances (p = 0.003) were significantly impaired in smoking AS patients (n = 35) as compared to non-smoking (n = 40). Systemic inflammation parameter, ESR was significantly higher in smoking AS patients than non-smoking (p = 0.03). The odds ratio of advanced modified Schober’s index, lateral lumbar flexion, fingertip-to-floor distance, chest expansion, and occiput-to-wall were significantly elevated in smoking AS patients as compared to non-smoking. Moreover, the smoking intensity correlated significantly with BASFI (r = 0.481, p = 0.005), cervical rotation (r = −0.401, p = 0.031), fingertip-to-floor distance (r = 0.485, p = 0.004), and occiput-to-wall distance (r = 0.473, p = 0.005) in the 35 smoking AS patients. The cigarette smokers in the Chinese AS patients have increased systemic inflammation and poor physical mobility. In addition, the higher smoking intensity in the AS smokers is associated with poor disease outcome, including functional ability and physical mobility. Thus, it is quite important for the physician to emphasize the association of smoking with poor disease prognosis in AS, and patients should be strongly recommended to avoid smoking cigarette.

Adult Still's disease patient developed thrombotic microangiopathy with diffuse digital gangrene

Adult onset Still’s disease (AOSD) is frequently manifested by the appearance of fever, skin rash, arthritis, sore throat, leucocytosis, hypertransaminasaemia, or hepatosplenomegaly (1). Severe lifethreatening complications, such as fulminant liver failure, acute respiratory distress syndrome, haemophagocytic syndrome, disseminated intravascular coagulation (DIC), or thrombotic microangiopathy (TMA) have been reported (2–4). We report here the case of an ASOD patient with pulmonary arterial hypertension (PAH) who developed TMA with diffuse digital gangrene in 2005 while the AOSD was still active. After immediate, aggressive treatment with pulse methylprednisolone and plasma exchange, progression of digital gangrene stopped, haemolytic anaemia and thrombocytopaenia gradually recovered. Our 42-year-old female was diagnosed with AOSD in October 1998 with the manifestations of arthritis, salmon-like skin rash, fever (up to 39.8 C̊), hyperferritinaemia (1134; normal 9–90 ng/mL), splenomegaly, and leucocytosis [white blood cell (WBC) count: 23.3610/L], fulfilling the diagnostic criteria proposed by Yamaguchi et al (1). At that time serum rheumatoid factor (RF) and anti-nuclear antibodies (ANA) were negative. Infection, malignancy, or other autoimmune diseases including Sjögren’s syndrome, systemic lupus erythematosus (SLE), and rheumatoid arthritis were also excluded after extensive studies. The patient then took prednisolone and nonsteroidal anti-inflammatory drugs (NSAIDs) irregularly but the disease activity of AOSD always remained active. Because of progressive exertional dyspnoea, pulmonary arterial hypertension (PAH) was diagnosed in April 2003, with right ventricle systolic pressure of 80 mmHg as determined by echocardiography. Other aetiologies that might contribute to the development of PAH were excluded, including anti-phospholipid syndrome (APS), in which serum anti-cardiolipin antibodies and lupus anticoagulant were negative. She was then treated with methotrexate (15 mg/week), prednisolone (10–15 mg/day), Bosentan (250 mg/day), and furosemide. On 28 April 2005, the digits of all four limbs suddenly became gangrenous (Figure 1) and the patient was drowsy the next day. At that time her vital signs were 35.5 C̊, 106/63 mmHg (blood pressure), 120/min (pulse rate), and 26/min (respiratory rate). WBC count was 10.6610/L and platelet count was 87610/L. Haemoglobin fell from 11.1 to 9.1 g/dL within 2 days after the digital gangrene developed. Urinalysis showed mild proteinuria. C-reactive protein was 12 mg/dL and erythrocyte sedimentation rate was 47 mm/h. A peripheral blood smear revealed many fragmented

Bone morphogenetic proteins and Dickkopf-1 in ankylosing spondylitis

Objectives: To determine bone morphogenetic proteins (BMPs) and Dickkopf homologue-1 (Dkk-1) levels in ankylosing spondylitis (AS). Method: Serum BMPs and Dkk-1 were measured in 72 AS patients and 30 healthy controls. For AS patients, we recorded the demographic data, disease activity, functional index, and global assessment with questionnaires, and image changes with roentgenography. We also measured human leucocyte antigen-B27 and systemic inflammatory reactants. Results: BMPs were higher but Dkk-1 was significantly lower in AS patients than in controls. Dkk-1 was higher in AS patients who received non-steroidal anti-inflammatory drugs (NSAIDs) regularly in the past year (p = 0.001). Serum BMP-7 level and the BMP-7/Dkk-1 ratio correlated significantly with sacroiliitis severity, Bath Ankylosing Spondylitis Radiology Index (BASRI)-total, modified Stoke Ankylosing Spondylitis Spinal Score, and disease duration. There were also significant positive correlations among serum levels of BMP-2, -4, and -6, BASRI-total, and disease duration (p < 0.05). However, BMP-2/Dkk-1 was only significantly correlated with disease duration. The calculated area under the standard receiver operating characteristics curve suggested that BMP-2/Dkk-1 and serum BMP-2 are good indicators to predict disease activity, functional index, and patient global assessment in AS patients. Conclusion: BMPs and BMPs/Dkk-1 were significantly correlated with disease activity, and radiological and functional indices in AS patients. Dkk-1 was lower in AS patients than in controls. Among AS patients, Dkk-1 was higher in those taking NSAIDs regularly. BMP or Dkk-1 may be taken as a biomarker for disease severity or a treatment outcome predictor in AS, but this needs further study.

Serum levels of matrix metalloproteinase‐3 in undifferentiated spondyloarthropathy

Spondyloarthropathy (SpA) is a family of chronic arthritis, characterized by inflammatory back pain, peripheral arthritis, and enthesitis (1). SpA comprises at least five major subtypes, including ankylosing spondylitis (AS), reactive arthritis (ReA), psoriatic arthritis (PsA), arthritis associated with inflammatory bowel disease (IBD), and undifferentiated SpA (uSpA; similar features to SpA but not fulfilling any of the previous disease categories). Serum matrix metalloproteinases-3 (MMP-3) has recently been shown to be a potential marker of disease activity in SpA patients, especially those with AS (2–4). 326 Letters

Invasive aspergillosis in patients with systemic lupus erythematosus: a retrospective study on clinical characteristics and risk factors for mortality

Objective The objective of this paper is to analyze the clinical features, outcomes, mortality risk factors, and all-cause mortalities of invasive aspergillosis (IA) in patients with systemic lupus erythematosus (SLE). Methods Medical records were reviewed to identify SLE patients with IA from January 2006 to June 2017, at Taipei Veterans General Hospital, Taiwan. A total of 6714 SLE patients were included. Clinical/laboratory parameters and treatment outcomes were analyzed. Results Four patients (19.0%) had definite and 17 had probable (81.0%) IA. Seven patients (33.3%) survived and 14 died (66.7%). Concurrently, there were 19 pneumonias (90.5%), 17 cases of other infections (81.0%), eight bacteremia (38.1%), nine cytomegalovirus (CMV, 42.7%) and six Candida (28.6%) infections. In all 55 blood cultures, 38 (69.1%) yielded gram-negative bacilli, of which carbapenem-resistant A. baumannii accounted for eight (21.1%); 17 (30.9%) yielded gram-positive cocci, of which methicillin-resistant S. aureus accounted for six (35.3%); and vancomycin-resistant Enterococcus accounted for four (23.5%). Daily steroid dose ≥ 20 mg (hazard ratio (HR) 2.00), recent pulse steroid therapy (HR 2.80), azathioprine (HR 2.00), rituximab (HR 2.00), plasmapheresis (HR 2.00), acute respiratory distress syndrome (HR 2.00), concurrent infections (HR 5.667) and CMV viremia (HR 1.75) were higher in the fatality group. All p values were less than 0.05. Septic shock (n = 7, 50% in the fatality group) is the most common cause of mortality. Conclusions High daily steroid dosing, recent pulse steroid therapy, azathioprine, rituximab, concurrent infections, and CMV viremia were mortality risk factors for IA in SLE.

Anti-Tumor Necrosis Factor-α Therapy in Undifferentiated Spondyloarthritis (USpA)

Undifferentiated spondyloarthritis (USpA) include incomplete forms or early phases of definite seronegative spondyloarthritis (SpA) and cases of spondyloarthritis that remain undifferentiated. The treatment of SpA is more conditioned by the disease localization. Non-steroidal anti-inflammatory drugs and disease-modifying antirheumatic drugs are the main therapeutic agents for the treatment of peripheral arthritis in USpA. Tumor necrosis factor-α (TNF-α) has been detected in sacroiliac joints of patients with SpA. Anti-TNF-α therapy has been shown efficacious in patients with active ankylosing spondylitis (AS) and psoriatic arthritis. Similar to these SpA subtypes, therapeutic options in USpA are also limited. In those cases in which severe symptoms persist despite these treatments or when there is a severe axial involvement, biologic therapy (such as anti-TNF-α agents) represent an effective choice. In these patients, anti-TNF-α treatment raises the important possibility of blocking a shift from USpA to differentiated forms of spondyloarthritis.