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author:("vili, Luis M.")
1.  Limited systemic sclerosis initially presenting with mesenteric panniculitis 
BMJ Case Reports  2014;2014:bcr2014206961.
Mesenteric panniculitis pertains to a group of uncommon disorders named sclerosing mesenteritis that present with different levels of inflammation and fibrosis of the small bowel mesentery. It is associated with abdominal surgeries, trauma, malignancies, infections and connective tissue diseases. To the best of our knowledge, no cases of sclerosing mesenteritis have been reported in patients with systemic sclerosis. We present a case of a 61-year-old woman who had incidental CT findings of mesenteric panniculitis. Diagnosis was confirmed by biopsy that showed fat necrosis. On further review she had a 1-year history of Raynaud's phenomenon. Physical examination showed sclerodactyly. She had elevated anticentromere antibodies and skin biopsy was consistent with scleroderma. She was diagnosed with limited systemic sclerosis and was treated with D-penicillamine. After 6 years of follow-up, the mesenteric panniculitis and systemic sclerosis both remained stable. This case highlights the importance of considering rheumatic diseases in the differential diagnosis of sclerosing mesenteritis.
doi:10.1136/bcr-2014-206961
PMCID: PMC4202032  PMID: 25326572
3.  Patient-reported outcome measures in a population of medically indigent patients with systemic lupus erythematosus in Puerto Rico 
SAGE Open Medicine  2016;4:2050312116670927.
Objective:
To determine patient-reported outcomes measures in indigent patients with systemic lupus erythematosus receiving their healthcare through the Puerto Rico government managed care system and compare these measures with non-indigent patients treated in a private fee-for-service setting.
Methods:
A cross-sectional study was conducted in a cohort of 98 Puerto Ricans with systemic lupus erythematosus. Patients from the public group (n = 40) were treated in a university-based specialized systemic lupus erythematosus clinic and the private group (n = 58) in a community-based rheumatology practice. Demographic and clinical features and patient-reported outcomes measures per LupusPRO instrument were determined. LupusPRO captures quality-of-life measures in 12 domains. Differences among study groups were examined using chi-square, Fisher’s exact, t-tests, and the Wilcoxon signed-rank test.
Results:
The mean (standard deviation) age of the study population was 44.9 (12.0) years; 94 (95.9%) were women. Patients in the public setting were younger and were more likely to have renal disease and elevated anti-double-stranded DNA antibodies, and being treated with azathioprine and cyclophosphamide. Patients from the public sector were more likely to have better quality-of-life measures in the LupusPRO domains of pain/vitality and coping. No significant differences were observed for the domains of lupus symptoms, physical health, emotional health, body image, cognition, procreation, lupus medications, desires/goals, social support, and satisfaction with medical care.
Conclusion:
Despite having a lower socioeconomic status and worse clinical status, systemic lupus erythematosus patients from the public sector had equal or better patient-reported outcomes measures than those treated in the private setting. This favorable outcome may be associated with the comprehensive healthcare received by these patients in a specialized lupus clinic.
doi:10.1177/2050312116670927
PMCID: PMC5036258  PMID: 27721978
Systemic lupus erythematosus; patient-reported outcomes; quality of life; underserved population; Puerto Rico
4.  Olecranon Bursitis Caused by Candida parapsilosis in a Patient with Rheumatoid Arthritis 
Case Reports in Rheumatology  2016;2016:2019250.
Septic bursitis is usually caused by bacterial organisms. However, infectious bursitis caused by fungi is very rare. Herein, we present a 68-year-old woman with long-standing rheumatoid arthritis who developed pain, erythema, and swelling of the right olecranon bursa. Aspiration of the olecranon bursa showed a white blood cell count of 3.1 × 103/μL (41% neutrophils, 30% lymphocytes, and 29% monocytes). Fluid culture was positive for Candida parapsilosis. She was treated with caspofungin 50 mg intravenously daily for 13 days followed by fluconazole 200 mg orally daily for one week. She responded well to this treatment but had recurrent swelling of the bursa. Bursectomy was recommended but she declined this option. This case, together with other reports, suggests that the awareness of uncommon pathogens, their presentation, and predisposing risk factors are important to establish an early diagnosis and prevent long-term complications.
doi:10.1155/2016/2019250
PMCID: PMC4993914  PMID: 27595032
5.  Genetic associations of leptin-related polymorphisms with systemic lupus erythematosus 
Clinical immunology (Orlando, Fla.)  2015;161(2):157-162.
Leptin is abnormally elevated in the plasma of patients with systemic lupus erythematosus (SLE), where it is thought to promote and/or sustain pro-inflammatory responses. Whether this association could reflect an increased genetic susceptibility to develop SLE is not known, and studies of genetic associations with leptin-related polymorphisms in SLE patients have been so far inconclusive. Here we genotyped DNA samples from 15,706 SLE patients and healthy matched controls from four different ancestral groups, to correlate polymorphisms of genes of the leptin pathway to risk for SLE. It was found that although several SNPs showed weak associations, those associations did not remain significant after correction for multiple testing. These data do not support associations between defined leptin-related polymorphisms and increased susceptibility to develop SLE.
doi:10.1016/j.clim.2015.09.007
PMCID: PMC4658308  PMID: 26385092
systemic lupus erythematosus; leptin pathway; gene polymorphisms
6.  Clinical Manifestations Associated with Overweight/Obesity in Puerto Ricans with Fibromyalgia Syndrome 
Journal of Obesity  2016;2016:1379289.
Objective. To determine the clinical manifestations associated with overweight/obesity in Hispanics from Puerto Rico with fibromyalgia syndrome (FMS). Methods. A cross-sectional study was performed in 144 patients with FMS (per American College of Rheumatology (ACR) classification criteria). Sociodemographic features, FMS-related symptoms, tender points (per ACR criteria), comorbidities, and FMS treatment were examined. BMI was calculated and patients were grouped into two categories: BMI ≤ 24.9 kg/m2 (nonoverweight/obese) and BMI ≥ 25 kg/m2 (overweight/obese). Bivariate and multivariate analyses were used to evaluate differences between the study groups. Results. The mean (standard deviation (SD)) age of patients was 50.2 (9.9) years; 95.1% were females and 75.7% were overweight/obese. In the bivariate analysis, overweight/obese patients were more likely to have self-reported memory impairment, anxiety, shortness of breath, and urinary frequency than nonoverweight/obese patients. In addition, the tender point count was higher in the overweight/obese group. In the logistic regression analyses, self-reported memory impairment and urinary frequency differences remained significant after adjusting for confounding variables. Conclusion. In this population of Puerto Ricans with FMS, overweight/obese patients experienced more FMS-related manifestations than nonoverweight/obese individuals. However, prospective studies are needed to confirm these associations and to elucidate if weight reduction interventions could favorably impact the severity of FMS.
doi:10.1155/2016/1379289
PMCID: PMC4739457  PMID: 26885384
7.  Infective endocarditis initially presenting with a dermatomyositis-like syndrome 
BMJ Case Reports  2014;2014:bcr2013200865.
Infective endocarditis (IE) may present with rheumatological manifestations such as myalgias, arthralgias, arthritis and back pain. However, muscle inflammation is rare. We present a case of a 68-year-old Hispanic man who presented with 1-month history of tiredness, weight loss, fever, myalgias, muscle weakness and dysphagia to solid food. On physical examination he had severe weakness in the proximal upper and lower extremities, and erythematous eruption involving the upper eyelids, neck and metacarpophalangeal joints. Creatine kinase levels were markedly elevated at 15 809 U/L. MRI of the right thigh revealed intermuscular and intramuscular oedema. Muscle biopsy showed acute necrotising suppurative perimyositis. Blood cultures were positive for methicillin-resistant Staphylococcus aureus. A transoesophageal echocardiogram revealed vegetations in the pulmonic valve. All clinical manifestations were resolved completely with broad-spectrum antibiotics. This case suggests that IE should be considered in the differential diagnosis of a patient presenting with inflammatory myopathy.
doi:10.1136/bcr-2013-200865
PMCID: PMC3902320  PMID: 24414182
8.  Clinical associations of anti-Smith antibodies in PROFILE: a multi-ethnic lupus cohort 
Clinical rheumatology  2015;34(7):1217-1223.
The aim of this study was to determine the association of anti-Sm antibodies with clinical manifestations, comorbidities, and disease damage in a large multi-ethnic SLE cohort. SLE patients (per American College of Rheumatology criteria), age ≥16 years, disease duration ≤10 years at enrollment, and defined ethnicity (African American, Hispanic or Caucasian), from a longitudinal US cohort were studied. Socioeconomic-demographic features, cumulative clinical manifestations, comorbidities, and disease damage (as per the Systemic Lupus International Collaborating Clinics Damage Index [SDI]) were determined. The association of anti-Sm antibodies with clinical features was examined using multivariable logistic regression analyses adjusting for age, gender, ethnicity, disease duration, level of education, health insurance, and smoking. A total of 2322 SLE patients were studied. The mean (standard deviation, SD) age at diagnosis was 34.4 (12.8) years and the mean (SD) disease duration was 9.0(7.9)years; 2127 (91.6 %) were women. Anti-Sm antibodies were present in 579 (24.9 %) patients. In the multivariable analysis, anti-Sm antibodies were significantly associated with serositis, renal involvement, psychosis, vasculitis, Raynaud's phenomenon, hemolytic anemia, leukopenia, lymphopenia, and arterial hypertension. No significant association was found for damage accrual. In this cohort of SLE patients, anti-Sm antibodies were associated with several clinical features including serious manifestations such as renal, neurologic, and hematologic disorders as well as vasculitis.
doi:10.1007/s10067-015-2941-y
PMCID: PMC4475431  PMID: 25896533
Anti-Smith antibodies; Clinical manifestations; Disease damage; Systemic lupus erythematosus
9.  Genetic Association of CD247 (CD3ζ) with SLE in a Large-Scale Multiethnic Study 
Genes and immunity  2015;16(2):142-150.
A classic T-cell phenotype in Systemic lupus erythematosus (SLE) is the downregulation and replacement of the CD3ζ chain that alters TCR signaling. However, genetic associations with SLE in the human CD247 locus that encodes CD3ζ are not well established and require replication in independent cohorts. Our aim was therefore to examine, localize and validate CD247-SLE association in a large multi-ethnic population. We typed 44 contiguous CD247 SNPs in 8 922 SLE patients and 8 077 controls from four ethnically distinct populations. The strongest associations were found in the Asian population (11 SNPs in intron 1, 4.99×10−4
doi:10.1038/gene.2014.73
PMCID: PMC4371129  PMID: 25569266
BMJ Case Reports  2013;2013:bcr2013008922.
Ehlers-Danlos syndrome (EDS) comprises a group of hereditary connective tissue disorders in which collagen synthesis and fibrogenesis are impaired. Patients with EDS type III have a bleeding tendency manifested by ecchymoses and haematomas. However, thrombotic events are rare in this entity. Herein, we present a 48-year-old Hispanic man with EDS type III who had recurrent cephalic vein thrombophlebitis and thrombosis, and brachial vein thrombosis. Tests for hypercoagulable disorders including antithrombin III activity, protein C activity, protein S activity, anticardiolipin antibodies, homocysteine levels, factor V Leiden mutation and prothrombin gene mutation were negative. The patient required long-term anticoagulation with warfarin. After 3 years follow-up, he did not present further thrombotic events. Clinicians should be aware that patients with EDS might be at risk for hypercoagulable disorders.
doi:10.1136/bcr-2013-008922
PMCID: PMC3702833  PMID: 23814193
BMJ Case Reports  2013;2013:bcr2013010117.
Cryoglobulinaemic vasculitis is characterised by immunoglobulin deposition at low temperatures. The most common manifestations are cutaneous involvement, arthralgias, Raynaud's phenomenon, peripheral neuropathy and renal disease. Myopathy is unusual and only a few cases have been reported. Here, we present a 31-year-old woman who developed progressive muscle weakness involving upper and lower extremities, dysphagia, paraesthesias and palpable purpura. Diagnostic studies revealed elevated creatine kinase, diffuse myopathic and sensorimotor axonal neuropathy on electromyography and nerve conduction studies, and inflammatory myopathy on muscle biospsy. Cryoglobulin levels were elevated on two occasions. She responded favourably to cyclophosphamide and high-dose corticosteroids. Cyclophosphamide was continued for 1 year followed by methotrexate. Prednisone was gradually tapered and discontinued 1 year later. She remained in clinical remission after 4 years of follow-up. This case suggests that cryoglobulinaemia should be considered in the differential diagnosis of a patient presenting with inflammatory myopathy.
doi:10.1136/bcr-2013-010117
PMCID: PMC3702929  PMID: 23737595
BMJ Case Reports  2013;2013:bcr2013008980.
Osteonecrosis is a relatively common comorbidity in systemic lupus erythematosus (SLE), but avascular necrosis in multiple sites is unusual. Multifocal osteonecrosis is defined as osteonecrotic lesions affecting three or more separate anatomic sites. We report a case of a 24-year-old woman diagnosed with SLE when she presented with mucocutaneous, haematological and mild renal manifestations. Initially, she was treated with prednisone and hydroxychloroquine and her condition remained stable. Two years later, she developed severe bilateral pretibial ulcers intractable to immunosuppressive therapy and broad-spectrum antibiotics. MRI of both legs disclosed osteonecrosis of the distal tibia, proximal tibia, distal fibula and talus bilaterally. She had elevated anticardiolipin antibodies for which she was treated with chronic anticoagulation resulting in complete healing of the leg ulcers and no further episodes of osteonecrosis. In addition to this case, we review the demographic, clinical and pharmacological features of 14 cases reported in the literature.
doi:10.1136/bcr-2013-008980
PMCID: PMC3645777  PMID: 23595183
Case Reports in Rheumatology  2015;2015:616787.
Rituximab is an anti-CD20 monoclonal antibody that has been used to treat several complications of systemic lupus erythematosus (SLE) including nephritis, cerebritis, and hematological disorders. Neutropenia is among the adverse events associated with rituximab; this usually occurs several weeks after therapy. However, early-onset neutropenia has been reported only in a few cases. Herein, we describe a 36-year-old Hispanic SLE woman who developed severe early-onset neutropenia (0.3 × 109/L) after the second weekly rituximab infusion (375 mg/m2 weekly × 4) given for nephritis and hemolytic anemia. She also had early-onset thrombocytopenia after rituximab therapy. Both hematological disorders resolved 12 days after the fourth and final dose. This case, together with few others, suggests that early-onset neutropenia may occur during rituximab therapy. Even though rituximab-induced neutropenia seems to be transient, it may predispose SLE patients to severe complications such as infections.
doi:10.1155/2015/616787
PMCID: PMC4342062  PMID: 25767732
BMJ Case Reports  2012;2012:bcr2012006907.
Euforia, a supplement containing a variety of natural ingredients, is widely used as an antioxidant and anti-inflammatory formula. It is not approved by the US Food and Drug Administration and its side effects are unknown. We report a 45-year-old woman with limited systemic sclerosis who presented with jaundice and marked elevation of serum transaminases. One month before, she started taking Euforia juice. A liver biopsy disclosed submassive hepatocellular necrosis with histopathological changes consistent with toxic hepatitis. The patient's symptoms resolved with cessation of Euforia. Six months later, she persisted with abnormal liver function tests, but these resolved 18 months after discontinuation of Euforia. The mechanism by which Euforia causes liver injury is unknown. Some ingredients contained in this supplement (green tea, Aloe vera, noni and goji) are linked to hepatic injury. To our knowledge, this is the first report of hepatotoxicity associated with Euforia.
doi:10.1136/bcr-2012-006907
PMCID: PMC4544356  PMID: 23257938
Purpose
Statins, which appear to have anti-inflammatory and immunomodulatory effects, may benefit patients with rheumatoid arthritis (RA). Our study sought to determine the association of statins use with disease activity and functional status in a group of patients with RA.
Methods
A cross-sectional study was performed in 209 Puerto Ricans with RA (per the 1987 classification criteria of the American College of Rheumatology). Demographic features, lifestyle-related behaviors, disease activity (per Disease Activity Score 28), comorbid conditions, functional status (per Health Assessment Questionnaire), pharmacologic therapy, and patients’ and physicians’ global assessments using visual analogue scales, were determined. Data were examined using univariate, bivariate, and multiple logistic regression analyses.
Results
The mean (standard deviation [SD]) age of the study population at study visit was 56.8 (13.5) years (range: 24–86 years); 175 patients (83.7%) were women. The mean (SD) disease duration was 10.4 (9.5) years (range: 0.0–44.0 years). Thirty-two (15.3%) patients were using statins at study visit, and 36 (17.2%) had used statins in the past. In the multivariable analysis, the current use of statins was associated with higher functional status (odds ratio 0.42, 95% confidence interval 0.22–0.80) than was nonuse, after adjusting for age, disease duration, arterial hypertension, coronary artery disease, and dyslipidemia. No association between either current or past use of statins and disease activity was found.
Conclusion
In this group of RA patients, the current use of statins was associated with a higher functional status; conversely, no association was found between statins use and disease activity. However, larger and longitudinal studies are required to confirm these findings.
PMCID: PMC4198336  PMID: 24665602
Rheumatoid arthritis; statins; disease activity; functional status; Puerto Ricans
Annals of the Rheumatic Diseases  2014;75(1):242-252.
Objectives
Systemic lupus erythematosus (SLE; OMIM 152700) is characterised by the production of antibodies to nuclear antigens. We previously identified variants in complement receptor 2 (CR2/CD21) that were associated with decreased risk of SLE. This study aimed to identify the causal variant for this association.
Methods
Genotyped and imputed genetic variants spanning CR2 were assessed for association with SLE in 15 750 case-control subjects from four ancestral groups. Allele-specific functional effects of associated variants were determined using quantitative real-time PCR, quantitative flow cytometry, electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (ChIP)-PCR.
Results
The strongest association signal was detected at rs1876453 in intron 1 of CR2 (pmeta=4.2×10−4, OR 0.85), specifically when subjects were stratified based on the presence of dsDNA autoantibodies (case-control pmeta=7.6×10−7, OR 0.71; case-only pmeta=1.9×10−4, OR 0.75). Although allele-specific effects on B cell CR2 mRNA or protein levels were not identified, levels of complement receptor 1 (CR1/CD35) mRNA and protein were significantly higher on B cells of subjects harbouring the minor allele (p=0.0248 and p=0.0006, respectively). The minor allele altered the formation of several DNA protein complexes by EMSA, including one containing CCCTC-binding factor (CTCF), an effect that was confirmed by ChIP-PCR.
Conclusions
These data suggest that rs1876453 in CR2 has long-range effects on gene regulation that decrease susceptibility to lupus. Since the minor allele at rs1876453 is preferentially associated with reduced risk of the highly specific dsDNA autoantibodies that are present in preclinical, active and severe lupus, understanding its mechanisms will have important therapeutic implications.
doi:10.1136/annrheumdis-2014-205584
PMCID: PMC4717392  PMID: 25180293
Systemic Lupus Erythematosus; Autoantibodies; Gene Polymorphism; B cells
Kottyan, Leah C. | Zoller, Erin E. | Bene, Jessica | Lu, Xiaoming | Kelly, Jennifer A. | Rupert, Andrew M. | Lessard, Christopher J. | Vaughn, Samuel E. | Marion, Miranda | Weirauch, Matthew T. | Namjou, Bahram | Adler, Adam | Rasmussen, Astrid | Glenn, Stuart | Montgomery, Courtney G. | Hirschfield, Gideon M. | Xie, Gang | Coltescu, Catalina | Amos, Chris | Li, He | Ice, John A. | Nath, Swapan K. | Mariette, Xavier | Bowman, Simon | Rischmueller, Maureen | Lester, Sue | Brun, Johan G. | Gøransson, Lasse G. | Harboe, Erna | Omdal, Roald | Cunninghame-Graham, Deborah S. | Vyse, Tim | Miceli-Richard, Corinne | Brennan, Michael T. | Lessard, James A. | Wahren-Herlenius, Marie | Kvarnström, Marika | Illei, Gabor G. | Witte, Torsten | Jonsson, Roland | Eriksson, Per | Nordmark, Gunnel | Ng, Wan-Fai | Anaya, Juan-Manuel | Rhodus, Nelson L. | Segal, Barbara M. | Merrill, Joan T. | James, Judith A. | Guthridge, Joel M. | Hal Scofield, R. | Alarcon-Riquelme, Marta | Bae, Sang-Cheol | Boackle, Susan A. | Criswell, Lindsey A. | Gilkeson, Gary | Kamen, Diane L. | Jacob, Chaim O. | Kimberly, Robert | Brown, Elizabeth | Edberg, Jeffrey | Alarcón, Graciela S. | Reveille, John D. | Vilá, Luis M. | Petri, Michelle | Ramsey-Goldman, Rosalind | Freedman, Barry I. | Niewold, Timothy | Stevens, Anne M. | Tsao, Betty P. | Ying, Jun | Mayes, Maureen D. | Gorlova, Olga Y. | Wakeland, Ward | Radstake, Timothy | Martin, Ezequiel | Martin, Javier | Siminovitch, Katherine | Moser Sivils, Kathy L. | Gaffney, Patrick M. | Langefeld, Carl D. | Harley, John B. | Kaufman, Kenneth M.
Human Molecular Genetics  2014;24(2):582-596.
Exploiting genotyping, DNA sequencing, imputation and trans-ancestral mapping, we used Bayesian and frequentist approaches to model the IRF5–TNPO3 locus association, now implicated in two immunotherapies and seven autoimmune diseases. Specifically, in systemic lupus erythematosus (SLE), we resolved separate associations in the IRF5 promoter (all ancestries) and with an extended European haplotype. We captured 3230 IRF5–TNPO3 high-quality, common variants across 5 ethnicities in 8395 SLE cases and 7367 controls. The genetic effect from the IRF5 promoter can be explained by any one of four variants in 5.7 kb (P-valuemeta = 6 × 10−49; OR = 1.38–1.97). The second genetic effect spanned an 85.5-kb, 24-variant haplotype that included the genes IRF5 and TNPO3 (P-valuesEU = 10−27–10−32, OR = 1.7–1.81). Many variants at the IRF5 locus with previously assigned biological function are not members of either final credible set of potential causal variants identified herein. In addition to the known biologically functional variants, we demonstrated that the risk allele of rs4728142, a variant in the promoter among the lowest frequentist probability and highest Bayesian posterior probability, was correlated with IRF5 expression and differentially binds the transcription factor ZBTB3. Our analytical strategy provides a novel framework for future studies aimed at dissecting etiological genetic effects. Finally, both SLE elements of the statistical model appear to operate in Sjögren's syndrome and systemic sclerosis whereas only the IRF5–TNPO3 gene-spanning haplotype is associated with primary biliary cirrhosis, demonstrating the nuance of similarity and difference in autoimmune disease risk mechanisms at IRF5–TNPO3.
doi:10.1093/hmg/ddu455
PMCID: PMC4275071  PMID: 25205108
BMJ Case Reports  2012;2012:bcr-2012-006507.
Patients with systemic lupus erythematosus (SLE) may develop thrombotic thrombocytopaenic purpura (TTP) or TTP-like illness manifested by microangiopathic haemolytic anaemia (MAHA) and thrombocytopaenia. The distinction between active SLE and TTP is difficult because these entities share similar clinical features. Drug-induced TTP caused by an immune-mediated reaction have been documented for several drugs. Herein, we report a middle-aged Hispanic woman with long-standing SLE, who developed a TTP-like illness characterised by MAHA and thrombocytopaenia after exposure to nitrofurantoin. The patient responded well to plasmapheresis and immunosuppressive therapy and has remained clinically stable after 18 months of follow-up. To our knowledge, this is the first case that reports the association between nitrofurantoin and a TTP-like presentation.
doi:10.1136/bcr-2012-006507
PMCID: PMC4543959  PMID: 22977056
Clinical rheumatology  2013;32(6):763-769.
The aim of this study was to determine the clinical outcome among indigent patients with rheumatoid arthritis (RA) in Puerto Rico receiving their healthcare in a managed care system, as compared to non-indigent patients treated in fee-for-service settings. A cross-sectional study was conducted in 214 Puerto Ricans with RA (per American College of Rheumatology classification criteria). Demographic features, health-related behaviors, cumulative clinical manifestations, disease activity (per Disease Activity Score 28), comorbid conditions, functional status (per Health Assessment Questionnaire, HAQ), and pharmacologic profile were determined. Data were examined using univariable and multivariable (logistic regression) analyses. The mean (standard deviation [SD]) age of the study population was 56.6 (13.5) years; 180 (84.1%) were women. The mean (SD) disease duration was 10.8 (9.6) years. Sixty-seven patients were treated in the managed care setting and 147 patients received their healthcare in fee-for-service settings. In the multivariable analyses RA patients treated in the managed care setting had more joint deformities, extra-articular manifestations, arterial hypertension, type 2 diabetes mellitus, cardiovascular events, fibromyalgia syndrome, and poorer functional status, while having a lower exposure to biologic agents than those treated in fee-for-service settings. Efforts should be undertaken to curtail the gap of health disparities among these Hispanic patients in order to improve their long term outcomes.
doi:10.1007/s10067-013-2167-9
PMCID: PMC3780563  PMID: 23314687
Rheumatoid arthritis; medically-indigent patients; Hispanics; Puerto Ricans; healthcare; managed care system; fee-for-service system
Background
Although a higher prevalence of osteoarthritis (OA) has been reported among diabetes mellitus (DM) patients, inconsistencies and limitations of observational studies have precluded a conclusive association.
Objective
To evaluate the association of hand or knee OA with DM in a population of Hispanics from Puerto Rico.
Methods
A cross-sectional study was performed in 202 subjects (100 adult DM patients as per the National Diabetes Data Group Classification, and 102 non-diabetic subjects). OA of hand and knee was ascertained using the American College of Rheumatology classification criteria. Sociodemographic characteristics, health-related behaviors, comorbidities, pharmacotherapy and DM clinical manifestations were determined. Multivariable logistic regression was used to evaluate the association of DM with hand or knee OA, and to evaluate factors associated with hand or knee OA among DM patients.
Results
The mean (standard deviation, SD) age for DM patients was 51.6 (13.1) years; 64.0% were females. The mean (SD) DM duration was 11.0 (10.4) years. The prevalence of OA in patients with DM and non-diabetics subjects was 49.0% and 26.5%, respectively (p<0.01). In the multivariable analysis, patients with DM had 2.18 the odds of having OA when compared to non-diabetic subjects (95% CI: 1.12–4.24). In a sub-analysis among DM patients, female patients were more likely to have hand or knee OA (OR [95% CI]: 5.06 [1.66–15.66]), whereas patients who did not use insulin alone for DM therapy were more likely to have OA (OR [95% CI]: 4.44 [1.22–16.12]).
Conclusion
In this population of Hispanics from Puerto Rico, DM patients were more likely to have OA of hands or knees than non-diabetic subjects. This association was retained in multivariable models accounting for established risk factors for OA. Among DM patients, females were at greater risk for OA, whereas the use of insulin was negatively associated.
doi:10.1097/RHU.0b013e31827cd578
PMCID: PMC3815459  PMID: 23319016
diabetes mellitus; osteoarthritis; metabolic disorders; musculoskeletal disorders
Lupus  2014;23(11):1133-1141.
Objective
To determine the extent of mitochondrial DNA (mtDNA) damage in systemic lupus erythematosus (SLE) patients compared to healthy subjects and to determine the factors associated with mtDNA damage among SLE patients.
Methods
A cross-sectional study was performed in 86 SLE patients (per American College of Rheumatology classification criteria) and 86 healthy individuals matched for age and gender. Peripheral blood mononuclear cells (PBMCs) were collected from subjects to assess the relative amounts of mtDNA damage. Quantitative polymerase chain reaction assay was used to measure the frequency of mtDNA lesions and mtDNA abundance. Socioeconomic-demographic features, clinical manifestations, pharmacologic treatment, disease activity, and damage accrual were determined. Statistical analyses were performed using t test, pairwise correlation, and Pearson’s chi-square test (or Fisher’s exact test) as appropriate.
Results
Among SLE patients, 93.0% were women. The mean (SD) age was 38.0 (10.4) years and the mean (SD) disease duration was 8.7 (7.5) years. SLE patients exhibited increased levels of mtDNA damage as shown by higher levels of mtDNA lesions and decreased mtDNA abundance as compared to healthy individuals. There was a negative correlation between disease damage and mtDNA abundance and a positive correlation between mtDNA lesions and disease duration. No association was found between disease activity and mtDNA damage.
Conclusion
PBMCs from SLE patients exhibited more mtDNA damage compared to healthy subjects. Higher levels of mtDNA damage were observed among SLE patients with major organ involvement and damage accrual. These results suggest that mtDNA damage have a potential role in the pathogenesis of SLE.
doi:10.1177/0961203314537697
PMCID: PMC4156531  PMID: 24899636
Systemic lupus erythematosus; disease activity; disease damage; mitochondrial DNA; mitochondrial dysfunction; oxidative stress
Arthritis care & research  2012;64(5):704-712.
Objective
To determine the clinical manifestations and disease damage associated with discoid rash in a large multiethnic systemic lupus erythematosus (SLE) cohort.
Methods
SLE patients (per ACR criteria), age ≥ 16 years, disease duration ≤ 10 years at enrollment, and defined ethnicity (African American, Hispanic or Caucasian), from a longitudinal cohort were studied. Socioeconomic-demographic features, clinical manifestations and disease damage [as per the Systemic Lupus International Collaborating Clinics Damage Index (SDI)] were determined. The association of DLE with clinical manifestations and disease damage was examined using multivariable logistic regression.
Results
A total of 2,228 SLE patients were studied. The mean (standard deviation, SD) age at diagnosis was 34.3 (12.8) years and the mean (SD) disease duration was 7.9 (6.0) years; 91.8% were women. Discoid lupus was observed in 393 (17.6%) of patients with SLE. In the multivariable analysis, patients with discoid lupus were more likely to be smokers and of African-American ethnicity, and to have malar rash, photosensitivity, oral ulcers, leukopenia and vasculitis. DLE patients were less likely to be of Hispanic (from Texas) ethnicity, and to have arthritis, end-stage renal disease (ESRD), and antinuclear, anti-dsDNA and anti-phospholipid antibodies. Patients with DLE had more damage accrual, particularly chronic seizures, scarring alopecia, scarring of the skin, and skin ulcers.
Conclusion
In this cohort of SLE patients, discoid lupus was associated with several clinical features including serious manifestations such as vasculitis and chronic seizures.
doi:10.1002/acr.21581
PMCID: PMC3559016  PMID: 22190480
discoid rash; systemic lupus erythematosus; disease damage
Objective
To determine the prevalence of systemic lupus erythematosus (SLE) and its associated comorbidities in patients from Puerto Rico using a database from a health insurance company.
Methods
The insurance claims submitted by physicians in 2003 to a health insurance company of Puerto Rico were examined. Of 552,733 insured people, 877 had a diagnosis of SLE (code 710.0) per the International Classification of Diseases, Ninth Revision (ICD-9). Demographic parameters and selected comorbidities were determined. The diagnosis of comorbities was ascertained using the ICD-9 code, the Current Procedural Terminology-4 (CPT-4) code (for disease specific procedures) and/or the Medi-Span Therapeutic Classification System (for disease specific pharmacologic treatment). Fisher exact test and Chi-square were used to evaluate differences between SLE patients groups.
Results
The mean age was 42.0 ± 13 and the female to male ratio was 12.5:1. The overall prevalence of SLE was 159 per 100,000 individuals. The prevalence for females was 277 per 100,000 women and for males it was 25 per 100,000 men. The most common comorbidities were high blood pressure (33.7%), osteopenia/osteoporosis (22.2%), hypothyroidism (19.0%), diabetes mellitus (11.6%) and hypercholesterolemia (11.6%). Overall, high blood pressure, diabetes mellitus, hypercholesterolemia, and coronary artery disease were more prevalent in SLE patients older than 54 years. Osteopenia/osteoporosis was more prevalent in women than in men.
Conclusions
The prevalence of SLE in Puerto Rico is very high. High blood pressure, diabetes mellitus, hypercholesterolemia, hypothyroidism and osteopenia/osteoporosis are common comorbidities in these patients. Identification and management of these comorbidities are critical for optimal medical care to this population.
doi:10.1097/RHU.0b013e318124a8af
PMCID: PMC3581330  PMID: 17762454
Systemic lupus erythematosus; prevalence; comorbidities; Puerto Rico
Ethnicity & disease  2010;20(1 0 1):S1-116-21.
Introduction
The clinical outcome and therapeutic response to immunosuppressive agents vary among patients with lupus nephritis of different ethnic populations. Thus, we evaluated the efficacy of two established treatment protocols for lupus nephritis (low-dose versus standard-dose cyclophosphamide) in Puerto Ricans with systemic lupus erythematosus (SLE).
Methods
A retrospective cohort of 49 adult patients with SLE treated with intravenous low or standard-dose cyclophosphamide for clinical or biopsy confirmed lupus nephritis was studied. Demographic parameters, clinical manifestations, autoantibodies and pharmacological treatments were determined prior to cyclophosphamide treatment. Renal parameters, disease activity, damage accrual and corticosteroid use were determined before and after treatment. Cyclophosphamide-associated adverse events were also examined. Univariable and bivariable analyses were used to evaluate group differences.
Results
Thirty-nine SLE patients received the standard-dose treatment and ten patients the low-dose therapy. Prior to cyclophosphamide infusion, demographic parameters, clinical manifestations, autoantibodies profile, disease damage and pharmacologic treatments were similar in both groups. Disease activity was higher in the low-dose group. After cyclophosphamide therapy, significant improvement of renal parameters (increase in the glomerular filtration rate and decrease in hematuria, pyuria, urinary cellular casts, proteinuria and hypertension) were observed only for patients that received the standard-dose therapy. Disease activity and corticosteroids requirement decreased in both groups after treatment. No differences were observed for adverse events associated with cyclophosphamide.
Conclusions
The standard-dose cyclophosphamide therapy appears to be more effective, and similar in terms of drug safety, than the low-dose regime for lupus nephritis in Puerto Ricans with SLE.
PMCID: PMC3572835  PMID: 20521398
systemic lupus erythematosus; lupus nephritis; cyclophosphamide; Hispanics; Puerto Ricans
Objectives
The aims of this study were to determine the outcome and predictors of renal disease progression in Puerto Ricans with systemic lupus erythematosus (SLE) initially presenting mild renal involvement.
Methods
A retrospective cohort of 61 SLE patients (per American College of Rheumatology classification) with mild renal involvement was studied. Mild renal disease was defined as glomerular filtration rate (GFR) ≥ 90 ml/min in the presence of proteinuria (> 0.25g/day, but < 3.5 g/day), hematuria, and/or urinary cellular casts. Demographic parameters, clinical manifestations, serologic markers, comorbidities, pharmacologic treatments, disease activity and damage accrual were determined at onset of renal disease. Factors associated with renal disease progression were evaluated using recurrent event survival analysis.
Results
Of 61 patients, 55(90.2%) were women. The mean [standard deviation (SD)] age at renal onset was 29(11.2) and the mean (SD) follow-up period was 5.1(3.4) years. Thirty-eight patients had a decline in GFR: Thirty-two had a mild decline (GFR = 60–89 ml/min), five developed moderate to severe renal insufficiency (GFR = 15–59 ml/min), and one evolved to end-stage renal disease (GFR< 15 ml/min). In the Cox model, low C4 levels and proteinuria > 0.5g/day were associated with an earlier decline in GFR.
Conclusions
The majority of SLE Puerto Rican patients initially presenting with mild renal involvement had a decrease in GFR after an average of five years of kidney disease, although most had a mild dysfunction. Low C4 levels and proteinuria were predictors of an earlier decline in GFR. The awareness of these factors may contribute to early identification of individuals at risk of renal deterioration.
doi:10.1097/RHU.0b013e31821c020a
PMCID: PMC3569025  PMID: 21617555
systemic lupus erythematosus; lupus nephritis; proteinuria; hypocomplementemia; Puerto Ricans; Hispanics

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