Long-term immunogenicity of a quadrivalent human papillomavirus vaccine in systemic lupus erythematosus.

OBJECTIVES: To evaluate the 5-year immunogenicity of a quadrivalent human papillomavirus (HPV) vaccine (GARDASIL) in patients with systemic lupus erythematosus (SLE). METHODS: Female SLE patients and controls, aged 18-35 years, who received GARDASIL in 2011 and sero-converted 12 months post-vaccination were followed for persistence of immunogenicity. Antibody measurement to HPV serotypes 6, 11, 16, 18 was repeated at 5 years. The rate of sero-reversion was compared between patients and controls, and factors associated with sero-reversion of the anti-HPV antibodies were studied. RESULTS: 50 SLE patients and 50 controls were vaccinated with GARDASIL. Among subjects who sero-converted at 1 year and consented for this study, antibodies to HPV serotypes 6, 11, 16 and 18 at 5 years were persistent in 24/27 (89%), 26/31 (84%), 32/34 (94%) and 24/25 (96%) of the SLE patients; and 32/33 (97%), 32/33 (97%), 32/32 (100%) and 23/24 (96%) of the controls, respectively. Antibody titers to HPV-6 and 16 were significantly lower in patients than controls. Seven (21%) SLE patients had sero-reversion of ≥1 anti-HPV antibodies. Sero-reverted patients experienced significantly more SLE flares, particularly renal, and had received significantly higher cumulative doses of prednisolone, mycophenolate mofetil and tacrolimus than those with persistent immunogenicity. The cumulative doses of prednisolone correlated inversely and significantly with the anti-HPV 6, 11, and 16 titers at 5 years. CONCLUSIONS: Immunogenicity of the quadrivalent HPV vaccine was retained in a high proportion of SLE patients at 5 year. Patients with more SLE renal flares and had received more immunosuppression were more likely to have sero-reversion of the anti-HPV antibodies. CLINICAL TRIAL REGISTRATION NUMBER: US ClinicalTrials.gov (NCT00911521 & NCT02477254).

Referral strategy for early recognition of axial spondyloarthritis: consensus recommendations from the Hong Kong Society of Rheumatology.

Low back pain is one of commonest problems prompting a visit to the family physician. Up to 5% of patients with chronic low back pain in the primary care setting are diagnosed as having spondyloarthritis, which includes the prototype disease ankylosing spondylitis. Making a diagnosis of ankylosing spondylitis is often delayed for years, leading to significant pain, impairment of quality of life, disability and productivity loss. A recent breakthrough in the treatment of spondyloarthritis is the anti-tumor necrosis factor-alpha biologics, which lead to rapid relief of pain and inflammation, and improvement in all clinical parameters of the disease. Patients with early spondyloarthritis often respond better than those with late established disease. With proper recognition of inflammatory back pain, and the use of magnetic resonance imaging, spondyloarthritis can now be diagnosed much earlier before features are evident on plain radiographs. Referral to the rheumatologist based on onset of back pain (> 3 months) before the age of 45 years, and an inflammatory nature of the pain, or the presence of human leukocyte antigen-B27, or sacroiliitis by imaging, have been confirmed in multi-center international studies to be a pragmatic approach to enable early diagnosis of spondyloarthritis. This referral strategy has recently been adopted by the Hong Kong Society of Rheumatology for primary care physicians and non-rheumatology specialists.

Combined low-dose mycophenolate mofetil and tacrolimus for lupus nephritis with suboptimal response to standard therapy: a 12-month prospective study.

OBJECTIVE: The objective of this paper is to evaluate the efficacy of combined mycophenolate mofetil (MMF) and tacrolimus (TAC) for lupus nephritis with suboptimal response to standard therapy. METHODS: Inclusion criteria for patients: (1) biopsy-confirmed active lupus nephritis; and (2) inadequate response to ≥ 2 immunosuppressive regimens. While prednisolone (≤ 10 mg/day) and angiotensin-converting enzyme inhibitors were continued, immunosuppressive agents were replaced by combined MMF (1 g/day) and TAC (4 mg/day). Patients were followed every 2 months for the clinical response and adverse events at 12 months. RESULTS: Twenty-one patients were recruited (20 women; age 35.8 ± 9.2 years; systemic lupus erythematosus (SLE) duration 111 ± 51 months). The histological classes of lupus nephritis were: IV/III (33%), V+III/IV (33%) and pure V (33%). The creatinine clearance (CrCl), urine protein-to-creatinine ratio (uP/Cr) and serum albumin was 82.4 ± 33 ml/min (<90 ml/min in 57%), 3.27 ± 1.5 and 30.1 ± 5.9 g/l, respectively. Thirteen (62%) patients had active urinary sediments and 17 (81%) patients had active lupus serology. At 12 months, eight (38%) patients had very good response, one (5%) patient had good response and five (24%) patients had partial response. Significant improvement in uP/Cr, albumin, complement C3 and anti-dsDNA titer, and stabilization of CrCl was observed in the responders. Thirty-three adverse events were reported in 18 patients: major infection requiring hospitalization (6%), infection not requiring hospitalization (27%), herpes infection (9%), diarrhea (12%), cramps (9%), dyspepsia (6%), transient increase in serum Cr (6%), alopecia (4%), facial twitching (3%), tremor (3%) and diabetes mellitus (3%). None of these had led to protocol withdrawal. CONCLUSIONS: Combined low-dose MMF and TAC is an option for lupus nephritis that fails to respond adequately to standard regimens, with two-thirds of patients improving after 12 months. Longer-term observation is needed to confirm its efficacy and safety.

Anti-müllerian hormone and ovarian reserve in systemic lupus erythematosus.

OBJECTIVE: To study the level of anti-müllerian hormone (AMH) and its relationship to age and previous exposure to cyclophosphamide (CYC) in patients with systemic lupus erythematosus (SLE). METHODS: Consecutive female patients ages 18-52 years who had menses at least once during the preceding 12 months and fulfilled ≥4 American College of Rheumatology criteria for SLE were recruited. AMH was determined using an enzyme-linked immunosorbent assay (ELISA) kit. Serum AMH levels were compared in patients with and without previous use of immunosuppressive agents. The relationship of the AMH level to the patient's age and CYC exposure was studied by linear regression and receiver operating characteristic (ROC) curve analysis. RESULTS: A total of 216 patients were studied (mean±SD age 35.1±10.1 years, mean±SD SLE duration 7.6±5.9 years). The mean±SD AMH level was significantly lower in patients previously exposed to CYC therapy than in those who had not been exposed after adjustment for age (1.58±2.92 versus 1.73±2.11 ng/ml; P=0.04). The median time interval between the AMH assay and the last dose of CYC administered was 6.7 years (interquartile range 3.4-8.5). AMH levels in users versus nonusers of other immunosuppressive agents, including mycophenolate mofetil, azathioprine, and the calcineurin inhibitors, were not statistically different. Linear regression revealed increasing age (beta -0.32, P=0.02) and each 5 gm of CYC exposure (beta -0.28, P=0.047) were independently associated with a lower AMH level. In patients ages 30 years and younger, a cumulative CYC dose cutoff of 5.9 gm yielded a sensitivity of 0.75 and a specificity of 0.80 for the prediction of undetectable AMH level on ROC curve analysis. CONCLUSION: AMH is a sensitive marker for ovarian damage due to previous CYC exposure in women with SLE.

Prognostically distinct clinical patterns of systemic lupus erythematosus identified by cluster analysis.

The objective of this study was to evaluate the patterns of clinical manifestations and their mortality in a large cohort of Chinese patients with systemic lupus erythematosus. The cumulative clinical manifestations of a large group of Chinese systemic lupus erythematosus patients who fulfilled at least four American College of Rheumatology criteria for systemic lupus erythematosus were studied. Patients were divided into distinct groups by using the K-mean cluster analysis. Clinical features, prevalence of proliferative lupus nephritis (World Health Organization class III, IV), autoantibody profile, and treatment data were compared and the standardized mortality ratios were calculated for each cluster of patients. There were 1082 patients included in the study (mean age at systemic lupus erythematosus diagnosis 30.5 years; mean systemic lupus erythematosus duration 10.3 years). Three distinct groups of patients were identified. Cluster 1 (n = 347) was characterized predominantly by mucocutaneous manifestations (malar rash, discoid rash, photosensitivity, oral ulcer) and arthritis but having the lowest prevalence of serositis, hematologic manifestations (hemolytic anemia, leukopenia, and thrombocytopenia), and proliferative lupus nephritis. Patients in cluster 2 (n = 409) had mainly renal and hematological manifestations but having the lowest prevalence of mucocutaneous manifestations. Pulmonary and gastrointestinal manifestations were significantly more frequent in cluster 2 than the other clusters. Cluster 3 patients (n = 326) had the most heterogeneous features. Besides having a high prevalence of mucocutaneous manifestations, serositis and hematologic manifestations, renal involvement, and proliferative lupus nephritis was also most prevalent among the three clusters. Patients in cluster 2 had a much higher standardized mortality ratio [standardized mortality ratio 7.23 (6.7-7.7), p < 0.001] than those in cluster 3 [standardized mortality ratio 1.27 (1.1-1.5), p = 0.005] and cluster 1 [standardized mortality ratio 0.95 (0.5-1.7), p = 0.86]. In conclusion, patients with systemic lupus erythematosus could be clustered into prognostically distinct patterns of clinical manifestations.

Annual incidence and standardized incidence ratio of cerebrovascular accidents in patients with systemic lupus erythematosus.

OBJECTIVES: To study the annual incidence and standardized incidence ratio (SIR) of cerebrovascular accident (CVA) in patients with systemic lupus erythematosus (SLE). SUBJECTS AND METHODS: The annual incidence of CVA from 1999 to 2007 in a longitudinal cohort of SLE patients was calculated each year and compared with that of the regional population within the same study period. Age-specific SIRs and outcome of CVA in SLE patients were also studied. RESULTS: In 2007, there were 490 SLE patients in our cohort. The mean annual incidence of CVA between 1999 and 2007 was 6.45/1000 patients and no obvious trend over time was observed. Of the 20 CVAs in patients with SLE, 18 (90%) were ischaemic stroke whereas two (10%) were haemorrhagic stroke. The mean SIR of all types of CVA in SLE patients was 2.02 [95% confidence interval (CI) 1.30-3.81; p = 0.002]. The SIR of ischaemic stroke decreased with age and the stroke incidence was no longer significantly higher than that of the population in patients aged >or= 60 years. Haemorrhagic stroke occurred mainly in younger SLE patients. The duration of hospitalization and the mortality rate for CVA was non-significantly higher in SLE than in non-SLE patients. CONCLUSIONS: The incidence of CVA in SLE remained constant over the 8 years between 1999 and 2007. Younger SLE patients are at substantially increased risk of CVA compared to age-matched population. The duration of hospitalization and the mortality rate for CVA are similar in SLE and non-SLE patients.

Effect of disease activity and damage on quality of life in patients with systemic lupus erythematosus: a 2-year prospective study.

OBJECTIVES: To examine the effect of disease activity and damage on health-related quality of life (HRQoL) in patients with systemic lupus erythematosus (SLE). METHODS: Consecutive SLE patients and matched controls were recruited for a study of HRQoL using the Medical Outcomes Study Short Form-36 (SF-36). SLE activity and damage was assessed by the Safety of Oestrogens in Lupus Erythematosus National Assessment SLE Disease Activity Index (SELENA-SLEDAI) and the American College of Rheumatology/Systemic Lupus International Collaborating Clinics (ACR/SLICC) Damage Index (SDI), respectively. Patients were prospectively followed for repeat HRQoL assessment at 2 years. The effects of cumulative disease activity and new damage on changes in SF-36 scores were evaluated. RESULTS: One hundred and fifty-five patients were studied (94% women; age 37.8+/-11.3 years; SLE duration 7.2+/-5.4 years). Fifty (32%) patients had active disease and 75 (48%) had organ damage at baseline. Compared with age- and gender-matched controls, SLE patients had lower SF-36 scores, and the difference remained significant after adjustment for income and education level. SF-36 scores in SLE patients correlated inversely with SDI but not with SELENA-SLEDAI scores. After 2 years, there was a significant drop in the mental component score of the SF-36. Regression analysis revealed that new damage was the only determinant for a reduction in SF-36 scores. Patients with higher cumulative disease activity had a greater drop in bodily pain and general health subscores. CONCLUSIONS: Impaired HRQoL is more common in SLE patients than controls, regardless of age, sex, education and poverty. Pre-existing organ damage is associated with poorer HRQoL and new damage predicts a further decline in HRQoL. Persistent disease activity is associated with deterioration in certain domains of the SF-36.

Risk and predictors of work disability in Chinese patients with systemic lupus erythematosus.

The aim of this study is to determine the risk and predictive factors for work disability in patients with SLE. A cross-sectional questionnaire study was performed to evaluate the employment status of a sample of consecutive Chinese patients with SLE. Demographic, socioeconomic data (age, gender, marital status, years of education and household income), employment status, self-reported fatigue score and disease characteristics (SLE duration, organ damage and disease activity) were collected. Work disability was defined by the failure to work due to SLE. The cumulative incidence of work disability since the time of SLE diagnosis was studied by a Kaplan Meier's plot, and factors predictive of work disability were studied by Cox regression. A total of 147 patients with SLE were studied (mean age = 39.4 +/- 11.3 years; 95% women). Among 105 patients who were working at the time of SLE diagnosis, 39 (37%) lost their ability to work as a result of SLE after a mean disease duration of 10.0 +/- 6.1 years. Twenty-two (56%) patients lost their work ability within 2 years of diagnosis of SLE. The self-reported reasons for job loss were musculoskeletal pain (87%), skin disease (26%), renal problem (21%), fatigue (85%), memory deterioration (51%), anxiety or depressive symptoms (74%), too frequent sick leave (10%) and long-term hospitalisation (10%). The cumulative risk of work disability was 36% at 5 years after SLE diagnosis. In a Cox regression model, age (HR = 1.06 [1.02-1.11] per year; P = 0.008), self-reported fatigue score (HR = 1.06 [1.01-1.10] per point; P = 0.01) and mean disease activity score in the preceding two years (HR = 1.20 [1.02-1.42] per point; P = 0.03) were independently associated with working disability. In all, 37% of this group of patients with SLE lost their work ability after having the disease for 10 years. More than 50% of these patients developed work disability within the first 2 years of SLE diagnosis. Older age, fatigue and more active disease were independent predictors of work disability.

Changes in body composition after glucocorticoid therapy in patients with systemic lupus erythematosus.

The aim of this study was to evaluate the changes in body composition after glucocorticoid treatment in patients with systemic lupus erythematosus (SLE). Consecutive SLE patients were recruited for serial measurements (baseline, months 2 and 6) of bone mineral density (BMD) and body composition [bone mineral content (BMC), fat and lean mass] by dual energy X-ray absorptiometry scan after high-dose oral glucocorticoid therapy. Factors correlated with changes in body composition were evaluated. 29 SLE patients were studied (age 39.7 +/- 11.5 years; 83% women with 29% postmenopausal; SLE duration 80.1 +/- 80 months). Fourteen patients (48%) were glucocorticoid-naive. The mean maximum daily dosage of prednisolone was 32.9 +/- 6.5 mg and the cumulative prednisolone dosage in 6 months was 2.7 +/- 0.7 g. At 6 months, a significant drop in BMC of the trunk (-5.0 +/- 2.2%; P = 0.04) and whole body (-1.2 +/- 0.4%; P = 0.002) compared with baseline was observed, and so was the BMD of the hip (-1.7 +/- 0.6%; P = 0.006) and whole body (-0.7 +/- 0.3%; P = 0.01). A significant increase in the fat mass of the trunk (+14.5 +/- 4.1%; P = 0.001) and limbs (+10.0 +/- 3.2%; P = 0.004), but a non-significant drop in lean mass of the trunk (-3.3 +/- 1.8%; P = 0.08) and limbs (-0.8 +/- 2.4%; P = 0.75) also occurred. The changes in whole body BMC correlated significantly with age (rho = -0.51; P = 0.02) and changes in total fat mass (rho = 0.44; P = 0.02) but not with lean mass (rho = -0.21; P = 0.27), gender, body mass index, smoking, prednisolone dosages or changes in BMD. In SLE patients, high-dose glucocorticoids lead to an early and rapid drop in bone mass, which is more serious in older patients and correlates with an increase in body fat.

A new strategy to replace the natural vitreous by a novel capsular artificial vitreous body with pressure-control valve.

PURPOSE: The current vitreous substitutes such as silicone oil, heavy silicone oil, and polymeric gels that are directly injected into vitreous cavity frequently cause severe intraocular complications. There is a very urgent need to find a more suitable artificial vitreous substitute for pars plana vitrectomy (PPV) surgery. METHODS: We have devised a novel capsular artificial vitreous using tailor-made silicone rubber elastomer. The novel device was implanted into the vitreous cavity of rabbit after PPV and the eye was examined by ophthalmoscopy, fundus photography, and tonometry during an 8-week treatment period. B-scan ultrasonography, electroretinogram (ERG), and histological studies by light microscopy were also performed at the end of 8 weeks. RESULTS: The novel artificial vitreous body consists of a thin vitreous-like capsule with a silicone tube-valve system. The capsule can be folded and implanted into vitreous cavity through 1.5 mm incision on sclera. Physiological balanced solution (PBS) was then injected into the capsule and inflated to support retina and control intraocular pressure (IOP) through the tube-valve system subsequently fixed under the conjunctiva. Experiments using rabbits showed that the novel vitreous body could effectively support the retina and apparently induced no significant pathological changes in the eye over 8 weeks. CONCLUSION: This approach may provide a new research strategy in the vitreous replacement technology. The novel artificial vitreous body device can effectively support retina, control IOP, and has good biocompatibility. It may be a good alternative to injecting artificial vitreous although its tamponade properties and usefulness still have to be proven in complex vitreoretinal diseases.

Risedronate for prevention of bone mineral density loss in patients receiving high-dose glucocorticoids: a randomized double-blind placebo-controlled trial.

UNLABELLED: This 6-month randomized double-blind placebo-controlled trial shows that risedronate is well tolerated and effective in improving lumbar spine BMD and reducing loss of BMD at the hips in patients receiving high-dose prednisolone. INTRODUCTION: Bisphosphonates have proven benefits in patients receiving chronic low-dose glucocorticoids. However, whether they are effective in preventing bone mineral density (BMD) loss during periods of high-dose glucocorticoid treatment is unclear. The objective of this paper is to study the efficacy of risedronate in preventing bone mineral density (BMD) loss in users of high-dose glucocorticoids. METHODS: Adult patients with medical diseases treated with high-dose prednisolone (>0.5 mg/kg/day) were randomized to receive risedronate (5 mg/day) or placebo for 6 months in a double-blind manner, along with elemental calcium (1,000 mg/day). Changes in BMD were studied. RESULTS: One hundred and twenty patients were recruited (82 women, age 42.8 +/- 14.3 years, 63% corticosteroid-naive, 30% women postmenopausal) and 103 completed the study. Baseline clinical characteristics and BMD were similar in the risedronate and placebo groups. At 6 months, a significant gain in spinal BMD was observed in the risedronate group (+0.7 +/- 0.3%; p = 0.03) but a drop was detected in the placebo group (-0.7 +/- 0.4%; p = 0.12). After adjustment for baseline BMD, age, gender, body mass index and cumulative prednisolone dosages, the inter-group difference in spinal BMD remained significant (1.4%; p = 0.006). Both groups had a significant drop in hip BMD, but the magnitude was greater in the placebo arm (-0.8 +/- 0.4% in risedronate versus -1.3 +/- 0.5% the in placebo). No new fractures developed. Subgroup analysis of corticosteroid-naive patients yielded similar results. Upper gastrointestinal adverse events were numerically more frequent in the risedronate group. CONCLUSIONS: Risedronate improves spinal BMD in users of high-dose glucocorticoids.

Renal damage in systemic lupus erythematosus: a comparative analysis of different age groups.

The objective of this study was to compare the frequency and severity of renal damage in systemic lupus erythematosus (SLE) with regard to the age of disease onset. Among 287 patients with new onset SLE diagnosed between 1991 and 2003 in our hospital, we identified those who fulfilled the American College of Rheumatology (ACR) criteria for renal involvement. Patients were categorized into childhood (age < 16 [corrected] years), adult (between 16 and 50 years) or late onset ( > or = 50 years) SLE. Clinical presentation of renal disease and cumulative renal damage as assessed by the renal domain of the Systemic Lupus International Collaborating Clinics/ACR damage index (SDI) were compared. A linear regression model was constructed to study the effect of age on renal damage. One-hundred and forty-nine patients were studied (134 women and 15 men), including 28 childhood, 107 adult and 14 late onset SLE patients. The mean age of SLE onset was 29.7 +/- 14 years. The prevalence of renal disease was 53% in childhood onset, 50% in adult onset and 58% in late onset SLE patients (P = 0.66). At renal disease presentation, late onset SLE patients had significantly lower creatinine clearance and were more likely to be hypertensive. Histological classes of nephritis and initial treatment response, however, did not differ significantly among the patients. After a mean observation of 80.3 months, 32 (21%) patients developed renal damage (renal SDI > or = 1). Late onset SLE patients had accrued more renal damage than the others. In a multiple regression model, age was not a significant determinant of renal damage after adjustment for baseline renal parameters, duration of renal disease, use of cyclophosphamide and initial treatment response. We concluded that the prevalence of renal disease was similar among SLE patients of different ages of onset. Late onset SLE patients had accrued more renal damage but age did not correlate with renal damage after adjustment for various clinical parameters.

Outcome of protein-losing gastroenteropathy in systemic lupus erythematosus treated with prednisolone and azathioprine.

OBJECTIVES: To report the efficacy of prednisolone and azathioprine (AZA) in the treatment of systemic lupus erythematosus (SLE)-related protein-losing gastroenteropathy (PLGE). METHODS: Between 1995 and 2002, 16 consecutive patients with SLE-related PLGE were treated with a regimen consisting of high-dose prednisolone (0.8-1 mg/kg/day for 6 weeks, then tapered to < or =10 mg/day) and AZA (2 mg/kg/day). Protein leakage from the gastrointestinal tract was confirmed by 99mTc-labelled human serum albumin scintigraphy and significant urinary loss of protein was excluded. Clinical response at 6 months of therapy was assessed and patients were followed for relapse of PLGE. RESULTS: Clinical characteristics of our patients at the time of PLGE were: age 36.2 +/- 8.7 (s.d.) yr; female:male ratio 15 : 1; mean SLE duration 29.6 +/- 65 months. Twelve patients had PLGE as the initial presentation of SLE. Fifteen (94%) patients had concomitant activity in other organs. All patients presented with oedema and eight patients (50%) had non-bloody diarrhoea. The mean serum albumin level was 22.8 +/- 5.7 g/dl. Protein leakage was at the small bowel in 11 (69%) patients and the large bowel in 5 (31%) patients. At 6 months of therapy, 14 (88%) patients had complete clinical response, 1 (6%) patient responded partially and 1 patient (6%) was treatment-refractory. Patients who responded were maintained on low-dose prednisolone (7.8 +/- 6.1 mg/day) and AZA (56.3 +/- 37 mg/day). Over a mean follow-up of 57.5 months, 1 (6%) patient had relapse of PLGE which responded to augmentation of prednisolone dosage. No patients developed alternative gastrointestinal diagnoses. Corticosteroid-induced psychosis, AZA-induced pancytopenia and herpes zoster occurred in three patients. CONCLUSION: PLGE is an uncommon manifestation of SLE. Treatment with a combination of prednisolone and AZA is effective and well tolerated.

Is antibody clustering predictive of clinical subsets and damage in systemic lupus erythematosus?

OBJECTIVE: To examine autoantibody clusters and their associations with clinical features and organ damage accrual in patients with systemic lupus erythematosus (SLE). METHODS: The study group comprised 1,357 consecutive patients with SLE who were recruited to participate in a prospective longitudinal cohort study. In the cohort, 92.6% of the patients were women, the mean +/- SD age of the patients was 41.3 +/- 12.7 years, 55.9% were Caucasian, 39.1% were African American, and 5% were Asian. Seven autoantibodies (anti-double-stranded DNA [anti-dsDNA], anti-Sm, anti-Ro, anti-La, anti-RNP, lupus anticoagulant (LAC), and anticardiolipin antibody [aCL]) were selected for cluster analysis using the K-means cluster analysis procedure. RESULTS: Three distinct autoantibody clusters were identified: cluster 1 (anti-Sm and anti-RNP), cluster 2 (anti-dsDNA, anti-Ro, and anti-La), and cluster 3 (anti-dsDNA, LAC, and aCL). Patients in cluster 1 (n = 451), when compared with patients in clusters 2 (n = 470) and 3 (n = 436), had the lowest incidence of proteinuria (39.7%), anemia (52.8%), lymphopenia (33.9%), and thrombocytopenia (13.7%). The incidence of nephrotic syndrome and leukopenia was also lower in cluster 1 than in cluster 2. Cluster 2 had the highest female-to-male ratio (22:1) and the greatest proportion of Asian patients. Among the 3 clusters, cluster 2 had significantly more patients presenting with secondary Sjögren's syndrome (15.7%). Cluster 3, when compared with the other 2 clusters, consisted of more Caucasian and fewer African American patients and was characterized by the highest incidence of arterial thrombosis (17.4%), venous thrombosis (25.7%), and livedo reticularis (31.4%). By using the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index, the greatest frequency of nephrotic syndrome (8.9%) was observed in patients in cluster 2, whereas cluster 3 patients had the highest percentage of damage due to cerebrovascular accident (12.8%) and venous thrombosis (7.8%). Osteoporotic fracture (11.9%) was also more common in cluster 3 than in cluster 2. CONCLUSION: Autoantibody clustering is a valuable tool to differentiate between various subsets of SLE, allowing prediction of subsequent clinical course and organ damage.

Effects of melatonin on the nitric oxide treated retina.

AIMS: Nitric oxide (NO) is a free radical which reportedly causes damage to living cells. This study evaluated the damaging effect of NO and the protection of melatonin on the retina in vivo. METHODS: Female Wistar rats (230-250 g) received two intraperitoneal injections of either melatonin (5 mg/kg) or vehicle alone. After general anaesthesia, the animals received 1 microl intravitreal injections of 0.9% saline and 1 mM sodium nitroprusside (SNP) into the right eye and the left eye, respectively. The animals were divided into two groups and then sacrificed after 24 hours (day 1) and 96 hours (day 4). The mean inner retinal layer thickness (mIRLT), the number of retinas expressing hyperchromatic (HC) nuclei in the inner nuclear layer (INL) and the apoptotic ganglion cell detection were compared. RESULTS: After 1 day, SNP significantly increased the mIRLT by 45% (p = 0.004), initiated more INL nuclear HC expression (p = 0.01) and apoptotic nuclei (p<0.05) compared with the control eyes. Injection of melatonin ameliorated these changes. On day 4, SNP demonstrated similar effects in all parameters on the retina. After the injection of melatonin, both INL HC expression and apoptotic ganglion nuclei in the SNP treated eyes were similar to the controls but the mIRLT was significantly greater than in controls (p = 0.006). CONCLUSION: Uncontrolled NO elevation caused morphological and nuclear changes in the retina. Melatonin significantly suppressed the NO induced increase in mIRLT, INL HC expression, and apoptotic ganglion cells on day 1, but not after day 4. Melatonin may have a protective role in the NO elevated retina.

Successful treatment of dermatomyositis-related rapidly progressive interstitial pneumonitis with sequential oral cyclophosphamide and azathioprine.

Interstitial lung disease (ILD) is a major complication of idiopathic inflammatory myopathies (IIM). We report the successful use of oral cyclophosphamide, followed by azathioprine maintenance, in the treatment of a patient with dermatomyositis-related rapidly deteriorating ILD, resistant to steroid. Prompt recognition and early aggressive immunosuppressive therapy may improve the outlook of this condition.

Three patients with lead poisoning following use of a Chinese herbal pill.

We report on three patients with lead poisoning following use of the Chinese herbal pill Bao ning dan, prepared by the same traditional Chinese medicine practitioner. The patients had varying degrees of exposure to Bao ning dan and different clinical manifestations. Blood lead concentrations did not correlate with clinical severity. Two patients received chelating therapy and blood lead concentrations subsequently rapidly decreased. One patient was managed conservatively and end-organ complications resolved gradually. With increasing use of traditional Chinese medicines, related adverse reactions are expected to become increasingly common. Practitioners of western medicine should remain alert to this possibility. A comprehensive drug review, including the use of herbal medicines, should form a routine part of medical history taking.