Hiok Hee Chng

International consensus on hereditary and acquired angioedema

*Allergy/Immunology, Respiratory Institute, Cleveland Clinic, Cleveland, Ohio yDepartment of Dermatology, Medical University of Graz, Graz, Austria zDepartment of Internal Medicine, Division of Immunology/Allergy, University of Cincinnati, Cincinnati, Ohio xDepartment of Rheumatology, Allergy, and Immunology Tan Tock Seng Hospital, Singapore jj Faculty of Medicine ABC, Sao Paulo, Brazil {Department of Dermatology, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan Department of Dermatology and Allergy, Allergie-Centrum-Charite, Charite e Universitatsmedizin Berlin, Germany **Department of Medicine, Division of Allergy/Immunology, National Jewish Health, Denver, Colorado yyDepartment of Medicine, Division of Rheumatology, Allergy, and Immunology, University of San Diego, San Diego, California

Hospitalization of individuals with systemic lupus erythematosus: characteristics and predictors of outcome

We performed a retrospective study of patients with systemic lupus erythematosus (SLE) admitted to hospital during a one-year period to describe characteristics associated with a poor outcome. There were 348 episodes of hospitalization of 223 individuals. The cause of admission was clinical flare of SLE (58%), infection (37%) and thromboembolic disease (8%). Readmission occurred in 35.8% and was associatedwith: active nephritis (HR 2.53, P < 0.01), flare of lupus (HR 2.0, P < 0.01) and more ACR criteria (HR 1.34 per extra criteria, P < 0.01). Individuals with multiple reasons for admission had a longer duration of stay [one four days (2,6), two five days (3,7) and three 9.5 days (6.5,14.5),P < 0.01]. There were 11 deaths (3.2% of admissions). The deaths were due to infection in nine cases (four with concurrent active SLE). In multivariate modelling, the main predictors of death were: previous multiple admissions (OR 12.4, P < 0.01), the presence of infection (OR 7.3, P < 0.01) and youngerage (OR 0.93 per increaseof one year, P 0.03). The presenceof active lupus nephritis and multisystem disease makes readmission more likely and individuals with multiple problems at the time of admission have longer hospital stays. Young patients with frequent readmissions and coexistent infections are most likely to die.

A comparative study of the clinical manifestations of systemic lupus erythematosus in Caucasians in Rochester, Minnesota, and Chinese in Singapore, from 1980 to 1992

OBJECTIVE To examine the relationship between ethnicity and major organ involvement at and after diagnosis in community-based cohorts of Caucasian and Chinese systemic lupus erythematosus (SLE) patients resident in Rochester, Minnesota, and Singapore, respectively. METHODS Clinical manifestations at and after diagnosis were compared in Caucasian and Chinese SLE patients. The association between ethnicity and disease manifestations at and after diagnosis was determined using logistic regression and Cox proportional hazards models, respectively, adjusting for the influence of demographic, socioeconomic, disease-related, and therapy-related factors. RESULTS At diagnosis, Caucasian SLE patients were 3 times more likely than Chinese SLE patients to have serositis (odds ratio [OR] 3.11, 95% confidence interval [CI] 1.01-9.71), nearly 7 times more likely to have a hematologic disorder (OR 6.95, 95% CI 2.20-21.97), and far less likely to have a malar rash (OR 0.19, 95% CI 0.07-0.54) or positive antinuclear antibodies (OR 0.11, 95% CI 0.03-0.52). Ethnicity was not associated with the prevalence of proteinuria or central nervous system (CSN) and other major organ involvement at diagnosis. After diagnosis, there was a trend toward less development of proteinuria and other major organ involvement in Caucasians (relative risk [RR] 0.47, 95% CI 0.19-1.15, and RR 0.22, 95% CI 0.05-1.04, respectively). CONCLUSION Chinese SLE patients are far less likely to have serositis or a hematologic disorder at diagnosis and may be more likely to develop proteinuria or CNS or other major organ involvement over the course of the disease, compared with Caucasian SLE patients. This may contribute to the increased mortality seen in Chinese SLE patients.

Association of a common complement receptor 2 haplotype with increased risk of systemic lupus erythematosus

A genomic region on distal mouse chromosome 1 and its syntenic human counterpart 1q23–42 show strong evidence of harboring lupus susceptibility genes. We found evidence of linkage at 1q32.2 in a targeted genome scan of 1q21–43 in 126 lupus multiplex families containing 151 affected sibpairs (nonparametric linkage score 2.52, P = 0.006). A positional candidate gene at 1q32.2, complement receptor 2 (CR2), is also a candidate in the murine Sle1c lupus susceptibility locus. To explore its role in human disease, we analyzed 1,416 individuals from 258 Caucasian and 142 Chinese lupus simplex families and demonstrated that a common three-single-nucleotide polymorphism CR2 haplotype (rs3813946, rs1048971, rs17615) was associated with lupus susceptibility (P = 0.00001) with a 1.54-fold increased risk for the development of disease. Single-nucleotide polymorphism 1 (rs3813946), located in the 5′ untranslated region of the CR2 gene, altered transcriptional activity, suggesting a potential mechanism by which CR2 could contribute to the development of lupus. Our findings reveal that CR2 is a likely susceptibility gene for human lupus at 1q32.2, extending previous studies suggesting that CR2 participates in the pathogenesis of systemic lupus erythematosus.

Low-dose pulse methylprednisolone for systemic lupus erythematosus flares is efficacious and has a decreased risk of infectious complications

We sought to test our clinical impression that using a low dose methylprednisolone pulse (MEP; µ1500 mg over 3 days) in treating flares of systemic lupus erythematosus (SLE) was effective and associated with fewer serious infections. We retrospectively studied SLE patients who received MEP between 1989 and 2000. A ‘low dose’ group of 26 patients who had received 1–1.5 g and a ‘high dose’ group of 29 patients who received 3–5 g of MEP were identified. SLEDAI scores and prednisolone doses were recorded at the time of MEP pulses and 6 months later. All serious infections (requiring admission and i.v. antibiotics) occurring during this 6 month period and their outcomes were recorded. Both groups had similar demographic data, initial SLEDAI scores, i.v. cyclophosphamide use, and SLE organ involvement. Despite high-and low-dose MEP being efficacious in controlling disease activity (lowering of SLEDAI scores and subsequent prednisolone dose) there were only nine episodes of serious infection in seven patients in the low-dose group compared with 20 episodes in 17 patients from the high-dose group (P ^ 0.04). In both groups a majority of infections (75 and 77% in the high-and low-dose groups) occurred in the first month after MEP. Those with a low serum albumin (< 20 g/l) had an increased risk of mortality (OR 44, 90% CI 6.19–312.98) and a trend towards greater numbers of infections. Low-dose MEP was effective in controlling SLE flares and associated with fewer serious infections than traditional high-dose MEP.

Acute lupus myocarditis: clinical features and outcome of an oriental case series.

Symptomatic myocarditis in systemic lupus erythematosus (SLE) is uncommon. We describe the clinical characteristics, management and outcomes of 11 SLE patients without any atherosclerotic risk factors, who presented with acute lupus myocarditis (ALM). All patients were female, 46% Chinese with mean age of 27 < 10 years at diagnosis of SLE. ALM was one of the initial manifestations of SLE in eight (73%) patients. The median duration from onset ALM to initiation of treatment was two weeks (range: 0.3-8). All had clinical feature of left ventricle dysfunction. The most common electrocardiographic feature was nonspecific ST/T wave changes (91%). Common echocardiographic findings included segmental wall motion abnormalities (81%) and decreased left ventricular ejection fraction (81%). Median SLE disease activity index at presentation was 16 (range: 4-30). All patients received high dose corticosteroids and 64% received intravenous pulse cyclophosphamide. There were two deaths (18%) from infections. The remaining nine survivors had no recurrence of ALM nor suffer any SLE-related damage (median SLICC damage score of 0), up to a median follow-up of four years (range: 2.5-10.1). Repeat echocardiography after six months or later showed normal LVEF in eight patients (89%). Early immunosuppressive therapy in ALM, with high dose corticosteroids and pulse intravenous cyclophosphamide, results in good cardiac outcome.

High-dose intravenous immunoglobulins in the treatment of toxic epidermal necrolysis: an Asian series.

Toxic epidermal necrolysis (TEN) is a severe, immune‐mediated, mucocutaneous reaction resulting in extensive keratinocyte apoptosis. High‐dose human intravenous immunoglobulins (IVIG) have been proposed as an effective treatment for TEN. Retrospective data from 8 patients with TEN and 4 patients with Stevens‐Johnson syndrome‐toxic epidermal necrolysis (SJS‐TEN) overlap treated with high‐dose IVIG were analysed. The total dose of IVIG administered was 2 g/kg body weight, with the exception of 2 patients who received a total dose of 1.5 g/kg body weight. Their mean age was 49.9 ± 18.8 years (range, 19 to 70 years). The mean time from the first sign of skin lesion or mucosal or epidermal detachment to commencement of IVIG was 8.7 ± 5.5 days (range, 3 to 22 days). Of the 11 patients who survived, the mean time to objective response was 3.6 ± 1.9 days (range, 2 to 8 days). The length of stay (LOS) in hospital was 20.4 ± 8.0 days (range, 10 to 37 days). The survival rate was 91.6%. One patient developed permanent mucocutaneous sequelae following TEN. There were no adverse reactions to IVIG. We conclude that high‐dose IVIG may be a safe and effective therapy for Asian patients with TEN.

Reversible acute gastrointestinal syndrome associated with active systemic lupus erythematosus in patients admitted to hospital

Patients with systemic lupus erythematosus (SLE) frequently have gastrointestinal (GI) symptoms. These are usually self-limiting and related to treatment side-effects or concurrent illness. However, abdominal pain may be due to bowel ischaemia which can lead to infarction and perforation. The likelihood of these serious events is increased in individuals with pain severe enough to require assessment in hospital or a SLEDAI score > 5. This paper describes a group of patients with active SLE and GI symptoms severe enough to require admission to hospital using a retrospectivereview of 52 SLE patients admitted to hospital with acute abdominal symptoms. The results showed that abdominal pain (87%), vomiting (82%) and diarrhoea (67%) had been present for a mean of 4.4 + 6.5 days and SLEDAI score was ≥4 in 83% of patients. CT scanning showed evidence of serositis and bowel involvementin 63% of patients who underwent this investigation.Intravenous(iv) fluids were used in 87%, parenteral steroids in 90% and iv cyclophosphamidein 31%. Most (n 51) were discharged well. Recurrence of GI symptoms occurred in 12 patients. The conclusions are that active SLE may manifest as an acute gastrointestinal syndrome. Early diagnosis, bowel rest, supportive medical therapy and treatment with corticosteroids and/or immunosupressives can result in a good outcome.

Immunological Characterization of the Spike Protein of the Severe Acute Respiratory Syndrome Coronavirus

ABSTRACT Severe acute respiratory syndrome (SARS) is a novel infectious disease caused by the SARS-associated coronavirus (SARS-CoV). There are four major structural proteins in the SARS-CoV, including the nucleocapsid, spike, membrane, and small envelope proteins. In this study, two sets of truncated fragments of spike protein were generated, the first were approximately 210-bp nonoverlapping fragments and the second were overlapping segments of 750 to 900 bp. From these 23 fragments, we identified a fragment of 259 amino acids (amino acids 441 to 700) that is a major immunodominant epitope. This fragment was highly expressed, and the purified fragment C could detect all 33 SARS patient serum samples tested, collected from 7 to 60 days after the onset of fever, but had no reactivity with all 66 healthy human serum samples tested. Thus, fragment C of spike protein was identified as an immunodominant antigen and could be used for serological detection of SARS-CoV infection.

Why generic and disease-specific quality-of-life instruments should be used together for the evaluation of patients with persistent allergic rhinitis

Background The importance of assessing health‐related quality of life (HRQL) of patients with allergic rhinitis (AR) has been well established, but the specific roles of rhinitis‐specific or general health instruments have not been delineated.