[show abstract][hide abstract] ABSTRACT: Systemic lupus erythematosus (SLE) is a chronic multisystem genetically complex autoimmune disease characterised by the production of autoantibodies to nuclear and cellular antigens, tissue inflammation and organ damage. Genome-wide association studies have shown that variants within the major histocompatibility complex (MHC) region on chromosome 6 confer the greatest genetic risk for SLE in European and Chinese populations. However, the causal variants remain elusive due to tight linkage disequilibrium across disease-associated MHC haplotypes, the highly polymorphic nature of many MHC genes and the heterogeneity of the SLE phenotype.
A high-density case-control single nucleotide polymorphism (SNP) study of the MHC region was undertaken in SLE cohorts of Spanish and Filipino ancestry using a custom Illumina chip in order to fine-map association signals in these haplotypically diverse populations. In addition, comparative analyses were performed between these two datasets and a northern European UK SLE cohort. A total of 1433 cases and 1458 matched controls were examined.
Using this transancestral SNP mapping approach, novel independent loci were identified within the MHC region in UK, Spanish and Filipino patients with SLE with some evidence of interaction. These loci include HLA-DPB1, HLA-G and MSH5 which are independent of each other and HLA-DRB1 alleles. Furthermore, the established SLE-associated HLA-DRB1*15 signal was refined to an interval encompassing HLA-DRB1 and HLA-DQA1. Increased frequencies of MHC region risk alleles and haplotypes were found in the Filipino population compared with Europeans, suggesting that the greater disease burden in non-European SLE may be due in part to this phenomenon.
These data highlight the usefulness of mapping disease susceptibility loci using a transancestral approach, particularly in a region as complex as the MHC, and offer a springboard for further fine-mapping, resequencing and transcriptomic analysis.
Annals of the rheumatic diseases 01/2012; 71(5):777-84. · 8.11 Impact Factor
[show abstract][hide abstract] ABSTRACT: A 69-year-old hypertensive woman presented with eye and mouth dryness, bilateral parotid gland enlargement, associated with anasarca and proteinuria. Family history was notable for malignancies including breast, nasopharyngeal and colon cancers. Physical exam disclosed hypertension, bilaterally enlarged, firm, non-tender parotid glands, fine bibasilar crackles and bipedal edema. Anti Ro/Sjögren's syndrome antigen A antibody was positive, with negative tests for anti La/Sjögren's syndrome antigen B and anti-nuclear antibody (ANA). Chest radiographs showed basal infiltrates. Sjögren's syndrome associated with glomerulonephritis and interstitial lung disease was diagnosed, and she received pulse methylprednisololone followed by oral prednisone with dramatic improvement. Two months later, while on prednisone 5 mg/day, she returned to the clinic with an enlarging fixed non-tender right breast mass. She underwent modified radical mastectomy of the right breast, and pathologic report revealed diffuse, small cell, non-Hodgkin's lymphoma of the breast; axillary lymph nodes were negative for tumor. She opted for alternative therapy and did not return to the clinic until 7 months later when she developed sudden monocular blindness in the right eye with no other systemic manifestations. Magnetic resonance imaging (MRI) revealed swelling and enhancement of intracanalicular and pre-chiasmatic segments of the right optic nerve and right side of the optic chiasm. Considerations were Devic's disease versus metastases. She received pulse methylprednisolone therapy (1 g/day for 3 days) with partial recovery of vision. She is scheduled for lymphoma chemotherapy to include rituximab.
International Journal of Rheumatic Diseases 05/2010; 13(2):164-70. · 1.65 Impact Factor
[show abstract][hide abstract] ABSTRACT: Systemic lupus erythematosis (SLE) patients are highly susceptible to infections.
We aim to present our experience regarding the manifestations and outcomes of Salmonella infections in a group of Filipino SLE patients.
This study reviewed the medical records of Filipino SLE patients with documented Salmonella infection seen at the Rheumatology Clinics of the University of Santo Tomas (UST) Hospital, Manila, Philippines from 2002 to 2009.
Included were 12 patients (11 female), with mean age of 25.75 years (range 11-53 years) and average SLE disease duration 4.45 years to Salmonella infection. Five had septic arthritis (knee in 4, hip in 1), one of whom had concomitant typhoid fever. Another two patients had typhoid fever only. Sepsis syndrome was noted in three. One patient each had soft tissue abscess and meningitis. Salmonella typhi was isolated in seven patients, Salmonella sp. in four, and S. enteritidis in one patient. Two patients developed acute respiratory distress syndrome (ARDS), another had mixed Salmonella and Klebsiella pneumonia. Eleven patients were on high-dose steroids for active disease, including one patient with antecedent first infusion of cyclophosphamide plus rituximab. Management consisted of antimicrobials and adjunct surgery for arthritis and abscess. Except for three patients with Salmonella sepsis, all other patients improved with appropriate therapy.
International Journal of Rheumatic Diseases 12/2009; 12(4):319-23. · 1.65 Impact Factor
[show abstract][hide abstract] ABSTRACT: To determine the prevalence of vitamin D inadequacy in a group of Filipino post-menopausal women with osteoporosis.
Seventy otherwise healthy post-menopausal Filipino women seen at the University of Santo Tomas Hospital, Section of Rheumatology, were diagnosed with osteoporosis by central dual-energy X-ray absorptiometry (DXA) technique. Levels of serum 25-hydroxyvitamin D were measured using enzyme-linked immunosorbent assay.
The mean age of this population was 70 +/- 8 years, with an average of 22 +/- 10 years since menopause, and mean body mass index (BMI) of 22 +/- 1 kg/m(2). Only 30% (21/70) were on calcium plus vitamin D supplementation. Overall serum 25-hydroxyvitamin D levels ranged from 48-128 nmol/L, with a mean of 87 +/- 20.48 nmol/L. Serum 25-hydroxyvitamin D levels were divided as follows: 80-140 nmol/L (adequate), 25-79 nmol/L (inadequate/insufficient), and < 25 nmol/L (deficient). Sixty-four percent (45/70) of subjects had adequate levels while 36% (25/70) had inadequate levels of 25-hydroxyvitamin D. There were no subjects with deficient levels of 25-hydroxyvitamin D. Fischer's exact test did not show a significant association between BMD and 25-hydroxyvitamin D (P = 0.4804).
Among this group of women with post-menopausal osteoporosis, only 36% had insufficient levels of 25-hydroxyvitamin D, with none of the subjects having deficient 25-hydroxyvitamin D levels. The majority (64%) had normal serum 25-hydroxyvitamin D levels--comparatively higher than that reported in the literature. These results suggest the possible contribution of factors other than vitamin D deficiency in post-menopausal Filipino women with osteoporosis.
International Journal of Rheumatic Diseases 09/2009; 12(3):225-9. · 1.65 Impact Factor
[show abstract][hide abstract] ABSTRACT: Infections including those of the central nervous system (CNS) are a major contributor to morbidity and mortality in systemic lupus erythematosus (SLE). This case series describes the etiology, contributing factors and outcomes of CNS infections in a group of Filipino patients with SLE.
Retrospective case series.
We reviewed the medical records of SLE patients diagnosed and confined for a CNS infection at the University of Santo Tomas Hospital in Manila, Philippines, from 1997 to 2007.
A total of 23 SLE patients (22 females) diagnosed with CNS infection were included in this study. The mean age was 25.8 years (range 12-51) at SLE diagnosis, and 30.9 years (range 14-58) at CNS infection, with a mean disease duration of 55 months (range 7-125). Nineteen cases (82.6%) were meningitis, and four (17.4%) were diagnoses of brain abscess. The etiologic agents were identified as Cryptococcus neoformans in seven (30.4%), Mycobacterium tuberculosis in seven (30.4%), Streptococcus pneumoniae in two (8.7%), Salmonella sp. in one (4.4%), Corynebacterium bovis with Actinomyces sp. in one (4.4%), and no isolate in five (21.7%). The average daily prednisone dose was 28.9 mg (range 0-60 mg); 10 patients had recently received pulse cyclophosphamide, and two were on mycophenolate mofetil at the time of infection. Most cases had active SLE; the lone patient in disease remission had S. pneumoniae meningitis post-splenectomy. The most common presentation was headache (100%) and fever (87%). The infection resolved completely in nine patients (39.1%), and resolved with sequelae in two patients (8.7%); 12 patients (52.2%) died.
We described the etiology and outcomes of CNS infections in a group of Filipino patients with SLE. Risk factors included active SLE in the majority of cases requiring moderate- to high-dose steroids and other immunosuppressants like cyclophosphamide. Although C. neoformans and M. tuberculosis were the most common etiologic agents, it is just as important to search for less common organisms which can produce disease in highly susceptible hosts. A high index of suspicion and early appropriate management are crucial to favorable outcome among these patients.
International Journal of Rheumatic Diseases 09/2009; 12(3):234-8. · 1.65 Impact Factor
[show abstract][hide abstract] ABSTRACT: Gout is a common rheumatologic condition with characteristic clinical presentations during the acute arthritis and chronic tophaceous stages. Because of this, there is a tendency to overlook rare but important conditions which are independent of, but can co-exist with gout. This case of severe hip and knee pain in a patient with tophaceous gout takes the reader on a problem-solving exercise which simulates the analytical processes and decisions made in the clinic.
International Journal of Rheumatic Diseases 04/2009; 12(1):57-60. · 1.65 Impact Factor
[show abstract][hide abstract] ABSTRACT: To review the current status of lupus registries, highlight the importance and evolution of registries in clinical lupus research, discuss substantial advances in the understanding of lupus through the use of registries, and discuss the future role of registries in terms of opportunities and challenges.
The literature reviewed originated from the PubMed database and was limited to adult disease in articles published before June 01, 2008. Keywords used in the PubMed search included the following terms: systemic lupus erythematosus, registry, cohort, and database. All articles were sorted and analyzed according to a template devised by the authors describing the different types of registries.
The most important features of a lupus registry are that they contain a large number of subjects and reflect a relatively real world environment for lupus patients. Data obtained from the lupus registries are essential for planning, designing, and conducting clinical lupus studies, especially those difficult, inappropriate, or even unethical to study in randomized controlled trials. Up to now, some well-conducted registries have received recognition for their contributions to lupus research through their focus on different goals: epidemiology, genetics, ethnic diversity, clinical features, or outcomes. Although they have evolved in design and study emphasis steadily, there are still many issues left to resolve. Apart from the development and future direction of the lupus registry, attention needs to be applied to normalizing the ethical and legal rules involving a lupus registry.
Lupus registries have demonstrated high standards and achieved much success through decades of effort, but they are still in an active state of evolution as they address more questions with greater clarity and sophistication.
Seminars in arthritis and rheumatism 12/2008; 39(4):224-45. · 4.72 Impact Factor
[show abstract][hide abstract] ABSTRACT: Basal C-reactive protein (CRP) is a heritable trait associated with long-term cardiovascular disease risk. Existing studies leave ambiguity over the key functional polymorphisms and fail to adjust for trans-acting effects. In a novel cohort of 285 Filipino systemic lupus erythematosus probands and their first-degree relatives, we quantified serum CRP and typed a dense map of CRP single-nucleotide polymorphisms (SNPs), along with SNPs in the interleukin-1 beta, interleukin-6 and apolipoprotein E genes. Ten CRP SNPs demonstrated association with basal CRP in a regression model (P=0.011-0.002). These delineated two haplotypes associated with high and low basal CRP expression (P=0.002). Differences in allele frequency were seen compared with Caucasian populations, enabling us to argue for an independent genetic effect from a phylogenetically distinct haplotype tagged by SNP rs1800947. We demonstrated an association between Apo epsilon 2 and higher basal CRP. Interleukin-6 genotype was associated with basal CRP, highlighting a role for acute-phase cytokines even in basal expression. Identifying these trans-acting variants may improve the use of basal CRP as a predictor cardiovascular risk, and increase our power to detect associations between CRP and disease.
Genes and immunity 04/2008; 9(2):153-60. · 4.22 Impact Factor
[show abstract][hide abstract] ABSTRACT: The aim of this study was to describe the presenting clinical manifestations and syndromes of Filipino patients on diagnosis of systemic lupus erythematosus (SLE). We performed a retrospective review of medical records of Filipino SLE patients included in the lupus database of the University of Santo Tomas (UST) in Manila, Philippines. All patients fulfilled the American College of Rheumatology criteria for SLE. The following data were recorded: (1) demographic profile, (2) clinical manifestations on SLE diagnosis, and (3) clinical syndromes prior to and during fulfillment of diagnostic criteria for SLE and disease interval from diagnosis of a clinical syndrome to SLE diagnosis. Clinical data of 1,070 patients entered into the UST lupus database as of October 2005 were analyzed. The average age at SLE diagnosis was 28.5 +/- 11.5 (range 5-71) years, with 1,025 female and 45 male subjects. The most common presenting manifestation was arthritis (68%), followed by malar rash (49%), renal involvement (47%), photosensitivity (33%), and oral ulcers (33%). The following clinical syndromes were recorded prior to or during SLE diagnosis: nephrotic syndrome (30%), undifferentiated connective tissue disease (UCTD) (22%), autoimmune hemolytic anemia (AIHA) (6%), and idiopathic thrombocytopenic purpura (ITP) (6%). Among these, AIHA preceded the diagnosis of SLE at the longest interval (20.3 +/- 30.6, range 1-194 months). In this large database of Filipino patients with SLE, the most common presenting manifestation was arthritis, with renal involvement occurring in almost 50%. Among the clinical syndromes, nephrotic syndrome was the most common, whereas AIHA recorded the longest interval preceding SLE diagnosis, at an average of 20.3 months. Our findings are similar to data from other countries and emphasize the broad range of manifestations of SLE. The findings also reinforce the need to establish and maintain SLE databases to enhance awareness, early diagnosis, and more efficient management of the disease.
Modern Rheumatology 02/2008; 18(2):161-4. · 1.72 Impact Factor
[show abstract][hide abstract] ABSTRACT: We describe the clinical features, therapies, and clinical course of pulmonary arterial hypertension (PAH) in a group of Filipinos with connective tissue diseases (CTDs). We retrospectively reviewed the records of patients diagnosed with PAH by a two-dimensional echocardiogram as a tricuspid regurgitant jet of more than 25 mmHg. All patients had underlying CTDs, defined by the American College of Rheumatology criteria, and were seen at the rheumatology clinics of the University of Santo Tomas Hospital and the St. Luke's Medical Center, Philippines. Of the 33 patients (32 women) included in the analysis, there were 14 patients with systemic lupus erythematosus (SLE), 12 with scleroderma, 5 with mixed connective tissue disease (MCTD), 1 with primary antiphospholipid syndrome (APS), and 1 with dermatomyositis. The average age at PAH diagnosis was 38 +/- 14 years (mean +/- SD), and the mean duration of illness from CTD to PAH diagnosis was 53 +/- 52 months. Twelve patients had died at the time of this report, with a median duration of 15 months (range 1-57 months) from PAH diagnosis to mortality: six of these had scleroderma, five with SLE, and one with APS. The following therapies were used in this group of patients: low molecular weight heparin, warfarin, calcium-channel blockers, aspirin, cyclophosphamide, bosentan, iloprost, and sildenafil. We have described the clinical profile of PAH in a group of Filipino patients with CTDs, most commonly SLE. Various forms of pharmacologic therapies were used among these patients. Mortality remains high, particularly among those with underlying scleroderma. Early recognition and treatment are crucial in order to provide a better outcome for these patients.
Modern Rheumatology 02/2007; 17(3):224-7. · 1.72 Impact Factor
[show abstract][hide abstract] ABSTRACT: Salmonella infections occur more frequently among immunocompromised patients such as those with systemic lupus erythematosus (SLE), with high propensity for extra-intestinal, including osteoarticular, involvement. Hemarthrosis following trauma, typhoid fever and septic arthritis of the knee developed in a 20-year-old female lupus patient with pulmonary hypertension, maintained on corticosteroids and warfarin. This article takes the reader through the clinical problem-solving process with an SLE patient whose illness is confounded by prolonged fever, with manifestations indistinguishable from that of either lupus activity and/or an infection. Early diagnosis, appropriate antibiotics, and if necessary, surgical intervention are essential principles of management to improve prognosis and prevent long-term disabilities such as destructive arthropathy.
APLAR Journal of Rheumatology. 11/2006; 9(4):342 - 346.
[show abstract][hide abstract] ABSTRACT: Aim: To provide an overview of the clinical manifestations, survival and causes of mortality of systemic lupus erythematosus (SLE) patients in Asia.Methods: Literature retrieval utilized the following sources: (i) computerized bibliographic database of the National Library of Medicine (MEDLINE 1986–2006) by PubMed; (ii) articles on SLE published in journals of national medical or rheumatology societies; and (iii) abstracts presented in national, regional and international rheumatology and SLE conferences. The available materials were cited to summarize and extrapolate data deemed most representative of each Asian country.Results: The average age at SLE diagnosis ranged from 24–33 years, with a ratio ranging from 8–28 females to one male. Cutaneous and musculoskeletal manifestations were the most frequently observed, ranging from 45–98% and 36–85%, respectively. Renal involvement ranged from 6–100% (overall), or 26–74% (excluding presenting manifestations, and data obtained from a renal centre). Survival rates ranged from 65–98% at 5 years, and 50–84% at 10 years, with a trend for improved survival in more recent reports. Infection and active SLE disease were the predominant causes of mortality, with renal and central nervous system involvement as the main organs involved at time of death.Summary: This overview substantiates the potential vastness of clinical material on SLE in Asia, and reinforces the need for concerted efforts to encourage more research designed to address special issues and develop a more efficient health care delivery system tailored to the Asian lupus patient.
APLAR Journal of Rheumatology. 11/2006; 9(4):336 - 341.
[show abstract][hide abstract] ABSTRACT: Objective: To obtain reference values of bone mineral density (BMD) for Filipino women in order to make a population-specific diagnosis of osteoporosis.Method: Sudy design: Cross-sectional. Setting: Osteoporosis Unit, Joint and Bone Center, Section of Rheumatology and Clinical Immunology, Department of Medicine, University of Santo Tomas Hospital, Manila, Philippines. Participants: 442 healthy Filipino women volunteers recruited from the outpatient department, Rheumatology and Clinical Immunology Clinic of the University of Santo Tomas Hospital and from within the University of Santo Tomas campus. Subjects with known underlying illness or conditions or intake of drugs that predispose to osteoporosis were excluded from the study. Intervention: Bone mineral density (BMD) measurements, expressed in grams per square centimenter of the lumbar spine, non-dominant femur and non-dominant forearm were done in 442 consecutive healthy Filipino women using the LUNAR DPX-IQ machine.Results: Means and standard deviations of BMD measurements at each site were calculated using Kwikstat software Version 3.6, Release 7. Results were grouped in decades to serve as reference per decade.Conclusion: Bone mineral density measurements of these 442 healthy Filipino women may serve as an initial reference guide for the diagnosis of osteoporosis in Filipino women.
APLAR Journal of Rheumatology. 04/2004; 7(1):30 - 37.