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Tang, Xiaolin. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2013. / Includes bibliographical references (leaves 132-144). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese.

From this series of studies, we conclude that microalbuminuria may represent a novel risk factor in SLE, and lupus patients are more susceptible to endothelial dysfunction caused by hyperhomocysteinemia. The use of antimalarial agents is beneficial for lupus patients with active disease on corticosteroid, and antioxidant vitamins are useful in lowering the oxidative stress markers but do not affect the endothelial function. The results highlight the importance of targeting the known modifiable risk factors in order to prevent premature atherosclerosis in SLE patients. / My first step was to elucidate the prevalence and metabolic abnormalities in SLE patients with microalbuminuria. Twenty percent of patients were found to have microalbuminuria, which was associated with higher mean arterial pressure, total plasma antioxidant and homocysteine levels. / Next, we recruited 12 SLE patients and 15 controls and gave them oral methionine loading to achieve acute hyperhomocysteinemia. After oral methionine loading, von Willebrand factor (vWF) levels increased significantly in both groups. The increase in vWF was apparently more pronounced in SLE (20%) compared to controls (8%). Fibrinogen binding to platelets increased significantly only in SLE patients. / Systemic Lupus Erythematosus (SLE) is a chronic inflammatory disease of unknown cause which can affect any organs. Studies have reported an increased prevalence of cardiovascular disease (CVD) in these patients. We performed a series of studies to elucidate the interaction between microalbuminuria, dyslipidaemia, hyperhomocysteinemia, oxidative stress and immune dysregulation from the underlying disease in order to understand the accelerated atherosclerotic process in SLE. / We then evaluated the effects of long-term antioxidant vitamins. The plasma malondialdehyde level was significantly decreased after treatment in the vitamin group. Other oxidative stress markers and antioxidant levels and endothelial function remained unchanged in both groups. / We then proceeded to study the relative effect of antimalarial agents on fasting lipid fractions in patients with active SLE. Total cholesterol, very low-density lipoprotein cholesterol, and low density lipoprotein cholesterol levels were significantly lower in patients taking antimalarial agents, particularly for those patients taking concomitant prednisone. In the last study, we demonstrated that hydroxychloroquine had no significant effect on the serum lipid profile in these lupus patients with mild or inactive disease. / Tam Lai Shan. / Adviser: Edmund K. Li. / Source: Dissertation Abstracts International, Volume: 68-03, Section: B, page: 1550. / Thesis (M.D.)--Chinese University of Hong Kong, 2006. / Includes bibliographical references (p. 178-214). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / School code: 1307.

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Patients were selected for the study on the basis of 1: A diagnosis of systemic Lupus Erythematosus according to the 1982 revised American Rheumatology Association criteria47 and 2: An adequate biopsy defined as containing at least six glomeruli. Patients were biopsied at Groote Schuur Hospital during the period 1978 to 1988 and the indications for renal biopsy were clinical based on laboratory results of renal function. Patients were followed between 1 and 120 months with a mean observation period of 34 months. The clinical records were scrutinised and the following pa·rameters were noted at the time of biopsy: age, sex, race, time from diagnosis to biopsy, serum urea, creatinine, creatinine clearence and urinary 24 hour protein. Using the latest serum urea, creatinine, creatinine clearence and / or 24 hour urinary protein where available, outcome was graded as: 1: An improvement in renal function 2: A stable renal function 3: Deterioration in renal function 4: Patient on dialysis 5: Death due to disease.

Introdução: A reativação do vírus latente da varicela-zoster ocasiona infecção por herpes zoster tanto em pacientes hígidos quanto em portadores de doenças crônicas e autoimunes, como lúpus eritematoso sistêmico juvenil (LESJ). As informações sobre infecção por herpes zoster (HZ), seus fatores de risco e desfecho no LESJ são limitadas devido à pequena representação desta complicação em publicações anteriores, e revela a necessidade de mais estudos visando contribuir para o melhor cuidado aos pacientes. Objetivos: Avaliar a prevalência de infecção por HZ em uma população expressiva de pacientes com LESJ, e sua possível associação com dados clínicos, demográficos, manifestações clínicas, alterações laboratoriais, atividade/dano cumulativo da doença, tratamento e evolução. Métodos: Estudo de coorte multicêntrico retrospectivo realizado em 10 serviços de Reumatologia Pediátrica do Grupo Brasileiro de Lúpus que incluiu 852 pacientes com LESJ. Os pacientes foram divididos em dois grupos: pacientes que tiveram infecção por HZ (avaliados durante episódio da infecção por herpes zoster) e pacientes sem infecção por HZ (avaliados na última consulta). Resultados: A frequência de infecção por herpes zoster foi 14,1% nos pacientes com LESJ, enquanto neuralgia pós-herpética e recorrência foram observadas em 5% dos pacientes. Ocorreu hospitalização em 61% dos pacientes e infecção bacteriana secundária em 13% dos pacientes. Quanto ao tratamento, 94% dos pacientes com LESJ recebeu aciclovir via intravenosa ou oral ao diagnóstico de infecção por HZ e nenhum deles teve complicação oftalmológica nem evoluiu para óbito. Após correção de Holm-Bonferroni para múltiplas comparações, duração da doença (1,58 vs. 4,41 anos, p<0,0001) e idade atual (13,9 vs. 17,0 anos, p < 0,0001) foram significantemente menores nos pacientes com infecção por HZ comparados aos pacientes sem esta complicação. As frequências de nefrite (37% vs. 18%, p < 0,0001), linfopenia (32% vs. 17%, p < 0,0001), hipertensão arterial (27% vs. 13%, p=0,001) e febre (35,5% vs. 5%, p < 0,0001), foram significantemente maiores nos pacientes com infecção por HZ. As medianas do score de atividade da doença/SLEDAI-2K [6,0 (0-35) vs. 2 (0-45), p < 0,0001], VHS [30 (3-120) vs. 18 (1-135) mm/1a hora, p < 0,0001] e PCR [3,05 (0-103) vs. 0,70 (0-364)mg/dL, p < 0,0001] foram significantemente maiores nos pacientes com infecção por HZ. Quanto ao tratamento, frequências do uso de prednisona (97% vs. 77%, p < 0,0001) e ciclofosfamida (20% vs. 5%, p < 0,0001) foram significantemente maiores nos pacientes com infecção por HZ, assim como medianas da dose atual de prednisona [20 (3 - 80) vs. 12,5 (1- 90) mg/dia, p<0,0001] e em mg/kg/dia [0,44 (0,5 - 3,8) vs. 0,24 (0,02 - 3,0), p < 0,0001]. A regressão logística mostrou quatro variáveis independentes associadas à infecção por HZ: duração da doença menor de 1 ano [OR 2.893 (IC 1.821-4.597), p < 0.0001], linfopenia < 1,500/mm3 [OR 1.931 (IC 1.183-3.153), p=0.009], uso de prednisona [OR 6.723 (IC 2.072-21.815), p=0.002] e uso de ciclofosfamida [OR 4.060 (IC 2.174-7.583), p < 0.0001]. Conclusões: A infecção por HZ foi evidenciada em 14% dos pacientes com LESJ. Este foi o primeiro estudo que identificou atividade da doença e tratamento do LESJ como principais fatores associados para infecção por HZ nos pacientes, que apresentou-se com distribuição típica dermatomal, baixa taxa de recorrência e complicações / Introduction: The latent varicella-zoster virus reactivation causes herpes zoster infection in healthy patients and patients with chronic and autoimmune diseases, such as childhood-onset systemic lupus erythematosus (cSLE). However, information about herpes zoster infection (HZI), risk factors and outcome in cSLE are limited due to the small representation of this complication in previous studies, and reveals the need for more studies to driving better treatments to affected patients. Objective: The aim of this multicenter study in a large childhood-onset systemic lupus erythematosus (cSLE) population was to assess the herpes zoster infection (HZI) prevalence, demographic data, clinical manifestations, laboratory, treatment and outcome. Methods: A retrospective multicenter cohort study (Brazilian cSLE group) was performed in 10 Pediatric Rheumatology services in São Paulo State, Brazil and included 852 cSLE patients. Patients were divided in two groups: patients with HZI (evaluated at the first HZI episode) and patients without HZI (evaluated at the last visit). Results: The frequency of HZI in cSLE patients was 14%. Hospitalization occurred in 61% and secondary bacterial infection in 13%. Intravenous or oral aciclovir was administered in 94% cSLE patients at HZI diagnosis. None of them had ophthalmic complication and death. Postherpetic neuralgia and recurrence rate occurred in 5%. After Holm-Bonferroni correction for multiple comparisons, disease duration (1.58 vs. 4.41 years, p < 0.0001) was significantly lower in HZI cSLE patients compared to those without HZI. Nephritis (37% vs. 18%, p < 0.0001), lymphopenia (32% vs. 17%, p < 0.0001) prednisone (97% vs. 77%, p < 0.0001), cyclophosphamide (20% vs. 5%, p < 0.0001) and SLEDAI-2K [6.0 (0-35) vs. 2 (0-45), p < 0.0001] were significantly higher in the former group. The median activity score of disease / SLEDAI-2K [6.0 (0-35) vs. 2 (0-45), p < 0.0001], ESR [30 (3-120) vs. 18 (1-135) mm/1st hour, p < 0.0001] and PCR [3.05 (0-103) vs. 0.70 (0-364) mg/dL, p < 0.0001] were significantly higher in patients with HZ infection. As for treatment, the frequency of prednisone use (97% vs. 77%, p <0.0001) and cyclophosphamide (20% vs. 5%, p < 0.0001) were significantly higher in patients with HZI, as well as the medians of the current dose of prednisone [20 (3-80) vs. 12.5 (1- 90) mg/day, p < 0.0001] and in mg/kg/day [0.44 (0.5 to 3.8) vs. 0.24 (0.02 to 3.0), P < 0.0001]. Logistic regression model showed that four independent variables were associated with HZI: disease duration < 1 year [OR 2.893 (CI 1.821-4.597), p < 0.0001], lymphopenia < 1,500/mm3 [OR 1.931 (CI 1.183-3.153), p=0.009], prednisone [OR 6.723 (CI 2.072-21.815), p=0.002] and cyclophosphamide use [OR 4.060 (CI 2.174-7.583), p < 0.0001]. Conclusion: HZI was identified in 14% of cSLE population. This was the first study that identified disease activity and treatment of cSLE as main factors associated to HZI, that presented as an early viral infection with a typical dermatomal distribution, low rate of recurrence and complications

Introdução: A reativação do vírus latente da varicela-zoster ocasiona infecção por herpes zoster tanto em pacientes hígidos quanto em portadores de doenças crônicas e autoimunes, como lúpus eritematoso sistêmico juvenil (LESJ). As informações sobre infecção por herpes zoster (HZ), seus fatores de risco e desfecho no LESJ são limitadas devido à pequena representação desta complicação em publicações anteriores, e revela a necessidade de mais estudos visando contribuir para o melhor cuidado aos pacientes. Objetivos: Avaliar a prevalência de infecção por HZ em uma população expressiva de pacientes com LESJ, e sua possível associação com dados clínicos, demográficos, manifestações clínicas, alterações laboratoriais, atividade/dano cumulativo da doença, tratamento e evolução. Métodos: Estudo de coorte multicêntrico retrospectivo realizado em 10 serviços de Reumatologia Pediátrica do Grupo Brasileiro de Lúpus que incluiu 852 pacientes com LESJ. Os pacientes foram divididos em dois grupos: pacientes que tiveram infecção por HZ (avaliados durante episódio da infecção por herpes zoster) e pacientes sem infecção por HZ (avaliados na última consulta). Resultados: A frequência de infecção por herpes zoster foi 14,1% nos pacientes com LESJ, enquanto neuralgia pós-herpética e recorrência foram observadas em 5% dos pacientes. Ocorreu hospitalização em 61% dos pacientes e infecção bacteriana secundária em 13% dos pacientes. Quanto ao tratamento, 94% dos pacientes com LESJ recebeu aciclovir via intravenosa ou oral ao diagnóstico de infecção por HZ e nenhum deles teve complicação oftalmológica nem evoluiu para óbito. Após correção de Holm-Bonferroni para múltiplas comparações, duração da doença (1,58 vs. 4,41 anos, p<0,0001) e idade atual (13,9 vs. 17,0 anos, p < 0,0001) foram significantemente menores nos pacientes com infecção por HZ comparados aos pacientes sem esta complicação. As frequências de nefrite (37% vs. 18%, p < 0,0001), linfopenia (32% vs. 17%, p < 0,0001), hipertensão arterial (27% vs. 13%, p=0,001) e febre (35,5% vs. 5%, p < 0,0001), foram significantemente maiores nos pacientes com infecção por HZ. As medianas do score de atividade da doença/SLEDAI-2K [6,0 (0-35) vs. 2 (0-45), p < 0,0001], VHS [30 (3-120) vs. 18 (1-135) mm/1a hora, p < 0,0001] e PCR [3,05 (0-103) vs. 0,70 (0-364)mg/dL, p < 0,0001] foram significantemente maiores nos pacientes com infecção por HZ. Quanto ao tratamento, frequências do uso de prednisona (97% vs. 77%, p < 0,0001) e ciclofosfamida (20% vs. 5%, p < 0,0001) foram significantemente maiores nos pacientes com infecção por HZ, assim como medianas da dose atual de prednisona [20 (3 - 80) vs. 12,5 (1- 90) mg/dia, p<0,0001] e em mg/kg/dia [0,44 (0,5 - 3,8) vs. 0,24 (0,02 - 3,0), p < 0,0001]. A regressão logística mostrou quatro variáveis independentes associadas à infecção por HZ: duração da doença menor de 1 ano [OR 2.893 (IC 1.821-4.597), p < 0.0001], linfopenia < 1,500/mm3 [OR 1.931 (IC 1.183-3.153), p=0.009], uso de prednisona [OR 6.723 (IC 2.072-21.815), p=0.002] e uso de ciclofosfamida [OR 4.060 (IC 2.174-7.583), p < 0.0001]. Conclusões: A infecção por HZ foi evidenciada em 14% dos pacientes com LESJ. Este foi o primeiro estudo que identificou atividade da doença e tratamento do LESJ como principais fatores associados para infecção por HZ nos pacientes, que apresentou-se com distribuição típica dermatomal, baixa taxa de recorrência e complicações / Introduction: The latent varicella-zoster virus reactivation causes herpes zoster infection in healthy patients and patients with chronic and autoimmune diseases, such as childhood-onset systemic lupus erythematosus (cSLE). However, information about herpes zoster infection (HZI), risk factors and outcome in cSLE are limited due to the small representation of this complication in previous studies, and reveals the need for more studies to driving better treatments to affected patients. Objective: The aim of this multicenter study in a large childhood-onset systemic lupus erythematosus (cSLE) population was to assess the herpes zoster infection (HZI) prevalence, demographic data, clinical manifestations, laboratory, treatment and outcome. Methods: A retrospective multicenter cohort study (Brazilian cSLE group) was performed in 10 Pediatric Rheumatology services in São Paulo State, Brazil and included 852 cSLE patients. Patients were divided in two groups: patients with HZI (evaluated at the first HZI episode) and patients without HZI (evaluated at the last visit). Results: The frequency of HZI in cSLE patients was 14%. Hospitalization occurred in 61% and secondary bacterial infection in 13%. Intravenous or oral aciclovir was administered in 94% cSLE patients at HZI diagnosis. None of them had ophthalmic complication and death. Postherpetic neuralgia and recurrence rate occurred in 5%. After Holm-Bonferroni correction for multiple comparisons, disease duration (1.58 vs. 4.41 years, p < 0.0001) was significantly lower in HZI cSLE patients compared to those without HZI. Nephritis (37% vs. 18%, p < 0.0001), lymphopenia (32% vs. 17%, p < 0.0001) prednisone (97% vs. 77%, p < 0.0001), cyclophosphamide (20% vs. 5%, p < 0.0001) and SLEDAI-2K [6.0 (0-35) vs. 2 (0-45), p < 0.0001] were significantly higher in the former group. The median activity score of disease / SLEDAI-2K [6.0 (0-35) vs. 2 (0-45), p < 0.0001], ESR [30 (3-120) vs. 18 (1-135) mm/1st hour, p < 0.0001] and PCR [3.05 (0-103) vs. 0.70 (0-364) mg/dL, p < 0.0001] were significantly higher in patients with HZ infection. As for treatment, the frequency of prednisone use (97% vs. 77%, p <0.0001) and cyclophosphamide (20% vs. 5%, p < 0.0001) were significantly higher in patients with HZI, as well as the medians of the current dose of prednisone [20 (3-80) vs. 12.5 (1- 90) mg/day, p < 0.0001] and in mg/kg/day [0.44 (0.5 to 3.8) vs. 0.24 (0.02 to 3.0), P < 0.0001]. Logistic regression model showed that four independent variables were associated with HZI: disease duration < 1 year [OR 2.893 (CI 1.821-4.597), p < 0.0001], lymphopenia < 1,500/mm3 [OR 1.931 (CI 1.183-3.153), p=0.009], prednisone [OR 6.723 (CI 2.072-21.815), p=0.002] and cyclophosphamide use [OR 4.060 (CI 2.174-7.583), p < 0.0001]. Conclusion: HZI was identified in 14% of cSLE population. This was the first study that identified disease activity and treatment of cSLE as main factors associated to HZI, that presented as an early viral infection with a typical dermatomal distribution, low rate of recurrence and complications