Healthcare encounters and outcomes of Filipino patients with Systemic Lupus Erythematosus managed at a Tertiary COVID-19 Referral Center

Objective@#The coronavirus disease 2019 (COVID-19) pandemic has limited healthcare delivery for patients with chronic diseases, including Systemic Lupus Erythematosus (SLE). This study aims to describe the outcomes of patients with SLE in a national COVID-19 referral center in the Philippines.@*Methods@#A review of records of all adult patients with SLE seen in the University of the Philippines-Philippine General Hospital (UP-PGH) from March 2020 to December 2021 was done. Data about patient characteristics, health encounters, and outcomes before and after the first visit during the study period were extracted. Descriptive statistics were employed.@*Results@#Our population of 403 patients was predominantly young (mean age 34.53 ± 11.14 years), female, and unemployed. This consisted of 370 known cases of SLE, 92 were diagnosed in institutions outside UP-PGH, and 33 new patients. Over the 22-month study period, there were 2,093 medical encounters, most of which were teleconsultations (81.70%). During an average gap of 53.6 ± 26.7 weeks between the last consultation and the first visit within the pandemic study period, 84 patients (22.70%) discontinued at least one of their SLE control medications, 68 (18.38%) patients developed a lupus flare, and 79 (21.35%) were hospitalized for various reasons. On their return to the rheumatology clinic during the pandemic, 37.47% were in lupus flare, 28.29% needed to be hospitalized, and 20 died. However, 86.75% of flares were controlled. During subsequent health encounters, 48 patients had a new flare (43 of these were controlled) and 20 died. The most common reason for hospitalization (n=160) was lupus disease flare and the most common cause of death (n=40) was pneumonia. Sixty patients acquired COVID-19 infection from which most recovered and four died.@*Conclusion@#Audio teleconsultation was the most common method used by our lupus cohort to interact with their doctors during the pandemic. There was an average of a year-long interruption in medical care for 62.70%. More than a third developed a disease flare and 15% acquired COVID-19 but outcomes were good in more than 85%. Despite the challenges posed by the pandemic, the majority of our lupus cohort who were able to continue their treatment had favorable outcomes.

Complete congenital heart block in the offspring of an asymptomatic woman with isolated high titer anti-ro antibody

@#Among pregnant women, 1-2% are anti-Ro positive and while half of them have symptoms of connective tissue disease, the rest are asymptomatic. The presence of anti-Ro is of concern because of the risk of congenital heart block in the child. We report the case of an asymptomatic 27-year-old G2P1(1001) woman, who presented with persistent fetal bradycardia in her 21st week of gestation (AOG) and was found to have elevated titers for anti-Ro (>320 U/ml). Hydroxychloroquine 200 mg/day and prednisone 10 mg/day were given from the 33rd week of gestation up until the delivery. At 37 weeks AOG, she delivered a live male neonate with a complete heart block. On the 6th day of life, the infant remained bradycardic, hence a pacemaker was inserted and heart rate maintained at 100-120 bpm. On subsequent follow-ups, the mother and child did not develop any systemic manifestations and the infant was thriving well. While a diseased condition may not be apparent in a pregnant anti-Ro positive woman, the risk of neonatal lupus (NL) is demonstrated in this patient’s case. This report illustrates how prenatal care of an asymptomatic woman led to the discovery of a fetal abnormality and served to prepare the family and the medical team to ably handle the birth and subsequent care of a neonate with NL.

A randomized controlled trial of center-based and home-based exercise programs among patients with rheumatoid arthritis

Background@#Rheumatoid arthritis (RA) patients benefit from aerobic and strengthening exercises. @*Objective@#To compare the effectiveness of a home exercise program against center-based aerobic and strengthening exercises on the grip strength, endurance, function, and fatigue among patients with RA. @*Methodology@#In this assessor-blind, randomized trial, 50 RA patients were assigned to either center-based physical therapy (CPT) or home exercise program (HEP) that included aerobic and strengthening exercises performed for four weeks. The grip strength, 6-minute walk test (6MWT), health assessment questionnaire disability index (HAQ-DI), and the multidimensional assessment of fatigue (MAF) index were determined at weeks 0 (baseline), 2 and 4 weeks.

Bamboo node as an unusual cause of Dysphonia in a Filipino patient with mixed Connective Tissue Disease

Introduction@#Bamboo node is a rare vocal cord pathology causing dysphonia among patients with autoimmune disorders. These “bamboo-joint-like” transverse deposits on the vocal cords interfere with the vibratory cycle during phonation leading to voice hoarseness. A review of Schwemmle from 1993-2009, showed seven cases of bamboo node among patients with mixed connective tissue disease (MCTD). With the patient’s consent, this case is presented to contribute to current knowledge about MCTD.@*Case Presentation@#A 36-year-old Filipino female developed voice hoarseness one year after she was diagnosed with MCTD. Videostroboscopic findings revealed bilateral bamboo nodes, vibratory defects, and amplitude abnormalities. Treatment with prednisone, methotrexate, hydroxychloroquine, along with voice rest and speech therapy resulted in normalization of amplitude, mucosal wave and vibratory behavior during repeat videostroboscopy.@*Conclusion@#To date, this is the first known case of bamboo nodes associated with MCTD in a Filipino patient. This case highlights the importance of properly investigating the symptom of hoarseness among patients with rheumatologic diseases. A multidisciplinary approach involving the rheumatologist, otorhinolaryngologist, and speech therapist play an important role in the complete care of this patient.

The association between D-dimer levels and thromboembolism, worsening severity, and mortality among hospitalized adults with COVID-19

Objective@#To assess the association between D-dimer and clinical outcomes in adults with COVID-19. @*Methods@#We reviewed published articles and preprints from MEDLINE, Cochrane Library, Cornell Open Access Publication (COAP), MedRxiv, and BioRxiv databases. We included cohort studies on the association between D-dimer and the outcomes of thromboembolism, mortality, and worsening severity among hospitalized adults with COVID-19. @*Results@#We found 25 observational studies on the association between D-dimer and the outcomes of thromboembolism, mortality, or worsening severity. There was an increased risk of thromboembolism (OR 5.61 [95% CI 3.97, 7.94]) with higher D-dimer levels across different COVID-19 severities. D-dimer levels are associated with higher in-hospital mortality (OR 5.57 [95% CI 2.74, 11.31]) and worsening severity manifesting as critical illness (OR 1.91 [95% CI 1.05, 3.48] to 2.58 [95% CI 1.57, 4.24]), disease progression (HR 2.846 [95% CI 2.10, 3.85]), or need for mechanical ventilation (HR 3.28 [95% CI 1.07, 10.10]). However, some methodological flaws, such as incomplete laboratory or follow-up data and concern on varied D-dimer cut-offs and definitions of worsening disease, raise some uncertainty in the widespread use of D-dimer as a prognostic marker. @*Conclusion@#A higher D-dimer value is associated with worse clinical outcomes among hospitalized adults with COVID-19 and may be a useful prognostic indicator.

Should anticoagulation be used in the treatment of severe COVID-19?

Background@#The progression of COVID-19 to its acute (pneumonia) phase occurs during the 7th to 14th day of illness. During this highly inflammatory phase, a proportion of patients with severe COVID-19 develop a hypercoagulable state associated with poor prognosis. Hence, anticoagulation is seen as a potentially beneficial intervention due to its antithrombotic effect, anti-inflammatory function, and anti-viral properties. @*Objective@#This review aims to determine the efficacy and safety of anticoagulation in severe COVID-19. @*Methods@#A rapid review was done on April 11, 2020 and updated on April 23, 2020. PubMed, MEDLINE, and medRxiv.org were searched. The review included studies on the association between the use of anticoagulants on top of other interventions, and disease progression and/or mortality among adults >18 years old with severe COVID-19 infection, as well as studies on patients with disseminated intravascular coagulopathy (DIC) of sepsis investigating bleeding complications with anticoagulant use. Four ongoing registered clinical trials on anticoagulants for COVID-19 were also found. @*Results@#Current evidence shows that the use of low-molecular weight heparin (LMWH) in COVID-19 is associated with the following: (1) improved surrogate markers for disease progression (increase in lymphocyte & platelet counts and decrease in D-dimer, fibrinogen degradation products, and IL-6); and (2) reduced 28-day mortality in high risk patients. Studies on DIC related to bacterial sepsis did not show significant increase in bleeding complications with anticoagulation. @*Conclusion@#The use of anticoagulants appears to be beneficial for severe COVID-19 due to a reduction in 28-day mortality and improvement in inflammatory and coagulation markers. However, these findings come from low-quality studies, and confirmation of the effect is needed through randomized controlled trials.

Should laboratory markers be used for early prediction of severe and possibly fatal COVID-19?

Key Findings@#Several laboratory tests are found to be associated with disease severity and mortality in COVID-19, and may be used to prognosticate patients and guide management. • Around 20% of COVID-19 patients develop severe illness that may require intensive care and lead to fatal complications. This necessitates prioritization of patients requiring urgent medical care before disease progression. • Certain laboratory markers (biomarkers) may reflect the processes involved in the clinical deterioration of infected patients. Hence, their use in the identification of patients at high risk of progression to severe disease or death has been investigated. • Current available evidence shows that the following laboratory abnormalities in a person with COVID-19, especially when found early during hospitalization, are associated with severe or critical disease or mortality: 1. Markers of organ dysfunction a. Reduced oxygen saturation b. Elevated lactic dehydrogenase (LDH) c. Elevated blood urea nitrogen (BUN) or serum creatinine d. Elevated cardiac troponin (cTnI) e. Elevated direct bilirubin, reduced albumin f. High radiographic score or CT severity score, or consolidation on CT scan 2. Marker of abnormal coagulation – D-dimer 3. Markers of immune dysfunction a. Elevated IL-6 b. Elevated C-reactive protein (CRP) c. Elevated neutrophils d. Reduced lymphocyte percentage e. Reduced CD4+ T lymphocytes 4. Secondary bacterial infection – Elevated procalcitonin • Proposed prediction models utilizing these markers, however, need further validation before they can be recommended for routine clinical use.

Outcomes of Hospitalizations Among Patients with Systemic Lupus Erythematosus in a Tertiary Government Hospital in the Philippines

@#INTRODUCTION: There is no documentation of the causes of hospitalization among lupus patients in the Philippines in recent times and this study hopes to fill in this knowledge gap. Thus, this study reports the outcomes of hospitalizations among patients with systemic lupus erythematosus (SLE) admitted at the charity wards of the University of the Philippines-Philippine General Hospital (UP-PGH). METHODS: A retrospective chart review was done on all admitted patients with SLE from January 2015 to December 2015 admitted at UP-PGH, the national referral center and tertiary training government hospital in Manila, Philippines. RESULTS: There were a total of 81 SLE patients meeting the inclusion criteria. SLE admission comprised 3.1% (138/4408) of admitted charity cases in our department. The most common reasons for hospitalizations are infection (64.1%), lupus activity (60.3%), and lupus activity with infection (47.4%). The mean duration of hospitalization was 12.4 (SD 8) days. Patients with organ damage from lupus were mostly able to fully recover (20%) while those admitted due to more than one reason mostly had partial recovery (95.2%). Infection is the top leading cause of death (6%). Serositis [OR 0.11, 95% confidence interval (CI) 0.02- 0.63] and number of ACR SLE criteria fulfilled on diagnosis (OR 0.47, 95% CI 0.22- 0.997) were likely to have poor outcome of hospitalization. The over-all cohort’s survival on admission was 100.0%, 98.8%, 97.4%, and 92.5% for one, two, six, and more than 15 days of admission, respectively. CONCLUSION: Our cohort confirms the results of previous studies suggesting that infection and disease activity were the top reasons for hospitalization among lupus patients whether living from emerging and developed nations. Indeed, the morbidity and mortality of our patients remains a great challenge not just among physicians but with the government and various stakeholders.

Posterior Reversible Encephalopathy Syndrome and Subarachnoid Hemorrhage After Methylprednisolone Pulse Therapy for a patient with Lupus Nephritis

Introduction@#Systemic lupus erythematosus (SLE) is a chronic inflammatory systemic disease that can affect any organ including the central nervous system (CNS). Subarachnoid hemorrhage (SAH) is one of its rare CNS manifestations. Posterior reversible encephalopathy syndrome (PRES), with features of headache, seizures, altered mental status, visual loss, and typical imaging findings, has recently been associated with SLE and immunosuppression, including use of high dose steroids. The patient was seen in University of the Philippines-Philippine General Hospital (UP-PGH), a tertiary training hospital in Manila, Philippines@*Case@#A 33-year-old female with lupus had PRES and SAH after methylprednisolone pulse therapy (MPPT) for nephritis. She presented with headache, hypertension and seizure. Initial cranial imaging showed hypodense areas in both parietotemprooccipital regions and small acute infarcts. She was intubated and treated with anti-convulsants for seizure; hydrocortisone and mycophenolate mofetil for SLE. She regained awareness on the seventh hospital day and was extubated. On the eleventh hospital day, she had fever, cough and was noted to be drowsy. She had increasing serum creatinine and decrease in urine output. Repeat cranial CT scan showed subarachnoid hemorrhage at the right sylvian fissure and better delineation of the previously described hypodensities (consistent with PRES). She was treated for hospital acquired pneumonia and underwent hemodialysis. Pneumonia was resolved and patient became conscious with no recurrence of neurologic symptoms. Consecutive outpatient visits showed a conscious and less edematous patient. Hemodialysis was eventually discontinued until she had normal creatinine with adequate urine output. Anti-seizure medications were also discontinued. Cranial CT scan a year later revealed normal brain parenchyma indicating resolution of previously noted hypodensities and subarachnoid hemorrhage.@*Conclusion@#There is a need to recognize PRES and differentiate it from irreversible neurologic conditions. With early identification and prompt intervention, permanent neurologic deficits may be prevented.

Effect of HMG-CoA Reductase Inhibitor Drugs (Statins) on Systemic Lupus Erythematosus Disease Activity: A systematic review and meta-analysis

Introduction@#Statins have been shown to have antiinflammatory and immunomodulatory effects. In vitro studies show that these drugs inhibit inflammatory cells, decrease the expression of major histocompatibility complex (MHC), decrease adhesion molecules and inflammatory cytokines (IL6 and IL10), that are also implicated in SLE pathogenesis. In terms of immunomodulary effects, animal studies demonstrate that statins exacerbate/trigger cellular apoptosis and induce a shift in the Th1/Th2 balance leading to B-cell reactivity and production of pathogenic autoantibodies. Whether statins have clinical effects in SLE have not been widely studied. In terms of disease activity, studies show contradicting results. The researchers aim to determine the effect of statins on the disease activity of SLE based on the best available evidence@*Methods@#A systematic literature search of PubMed, Scopus, and Cochrane databases was done with no date and language restrictions. Included studies were on adult SLE patients and randomized controlled trials that used statins as intervention and reported SLE disease activity as an outcome measure. Two reviewers did quality appraisal, risk bias assessment, and data extraction.@*Results@#Three studies met the eligibility criteria and were included in this review. Quantitative synthesis was done. The pooled analysis of these studies suggests that atorvastatin has no significant effect on disease activity using random effects model with an overall effect of 0.12 (P=0.90, 95% CI -1.65, 1.88).@*Conclusion@#Atorvastatin neither increased nor decreased SLE disease activity. Therefore possibly it can be safely given to SLE patients without the risk of triggering or exacerbating a flare.

Disease characteristics of Behcet’s Disease among Filipino patients seen in Rheumatology Clinics

Introduction@#Behcet's disease (BD) sometimes called behcet's syndrome or silk road disease is an immunemediated systemic vasculitis. This condition remains a clinical challenge for physicians. There are many reports, mostly case series and nationwide surveys, on clinical manifestations of BD from different parts of the world. In the Philippines where BD is rare and underreported, physicians might not be familiar with the clinical manifestations of this disease. The aim of this research is to describe the disease presentation of BD among Filipinos to increase awareness and avoid delay in diagnosis which might pose a threat for the development of irreversible, sometimes fatal complications.@*Methods@#A manual search was done for medical records with diagnosis of BD in the clinics of rheumatology staff of PGH. The diagnosis of BD was based on the 2006 International Criteria for BD. We noted the demographic data, clinical manifestations, results of ancillary procedures, treatment and outcomes. The study follows a descriptive design. @*Results@#There were 31 patients with the diagnosis of BD found from the manual search. Most of them were female (77%). The mean age at diagnosis was 38.6 years ± 10.4 (SD) and the mean time duration from onset of first symptom to diagnosis was 41 months (range three to 180 months). Three patients had a family member who also had BD (10%). The most common features of the disease were oral ulcers (94%), ocular manifestation (68%), and cutaneous disease (65%). The pathergy test was positive in 17%.The most common treatments prescribed were oral steroids (74%), colchicine (58%), and NSAIDs (48%). There was symptom control or improvement in a third of patients but there were still symptom recurrence in some. Thirteen patients (42%) had recurrent oral ulcerations while 23% had recurrence of skin lesions. Two of the patients (six percent) developed blindness. There was no death recorded. @*Conclusion@#There is an average delay of three years in the diagnosis of BD that hinders appropriate early treatment. Moreover, BD remains to be a clinical challenge for physicians. While a third of the cohort had good outcomes, half still had symptom recurrences and the occurrence of blindness in two patients underlines the potential of the disease to disable. We recommend expansion of the cohort to include the BD patients of other rheumatologists in the Philippines to have an idea on the actual prevalence and incidence of how this uncommon disease in our locality, and to have a better understanding of its clinical presentation and disease management in our country.