Severe hematologic manifestations among Filipino patients with systemic lupus erythematosus: A 5-year retrospective cohort study

@#<p style="text-align: justify;"><strong>Objective:</strong> Determination of the prevalence of severe hematologic manifestations among Filipino patients with systemic lupus erythematosus (SLE) and analysis of any association with organ involvement and serology.</p><p style="text-align: justify;"><strong>Methods:</strong> This cross-sectional study included SLE patients 19 years old and above seen at the UST Hospital from 2012 to 2017. Patients with severe hematologic manifestations (severe hemolytic anemia, severe thrombocytopenia, and Evans syndrome (ES)) were identified and their prevalence determined. Independent t-test was used to compare continuous variables. Categorical variables were measured using the chi-square test; odds ratios (OR) with their corresponding 95% confidence interval were calculated using the SPSS software version 21. This study has been approved by the Institutional Review Board.</p><p style="text-align: justify;"><strong>Results:</strong> Of the 253 patients (238 females, 94.07%), the mean age at diagnosis was 27.04 (SD 9.96) years. Severe hematologic involvement was noted in 12.26% (n=31); severe hemolytic anemia was the most prevalent (14, 5.53%), followed by severe thrombocytopenia (13, 5.14%) and ES (4, 1.58%). Higher prevalence of major organ involvement was observed among patients who manifest with severe hematologic disease. Severe thrombocytopenia was more likely to have cardiac involvement (OR 7.39, 95% CI 1.90 to 28.81, p=0.004). A higher prevalence of negative baseline anti-dsDNA serology was seen among patients who developed ES.</p><p style="text-align: justify;"><strong>Conclusion:</strong> Severe hematologic involvement was noted in 12.26% of Filipino SLE patients, with hemolytic anemia as the most frequently recorded. Severe thrombocytopenia was associated with cardiac involvement among these patients. Patients developing ES tend to have a negative anti-dsDNA serology.</p>

Neurology Case Series of Five Filipino Patients with Systemic Lupus Erythematosus

@#INTRODUCTION: Neuropsychiatric systemic lupus erythematosus (NPSLE) and central nervous system (CNS) infection are two significant complications of SLE where mortality is high. Differentiating the two diseases could help deliver appropriate and timely therapeutic strategies that impact mortality in patients with SLE particularly in cases where confusions due to overlapping symptoms delay early interventions. METHODS: We reviewed the medical records of SLE patients diagnosed and confined for a NPSLE at the University of Santo Tomas Hospital in Manila, Philippines, January 2015-December 2016. Informed consent was collected. CASE PRESENTATION: We report 5 cases of SLE patients (1 male; females) who presented between January 2015-December 2016 in a tertiary care hospital obtained from the SLE database of University of Santo Tomas (UST) Hospital Section of Rheumatology. All five patients were identified to have NPSLE with following chief complaints: (case 1: 22M) seven-day history of left-sided hemiparesis, (case 2: 22F) vomiting and generalized tonic-clonic seizures, (case 3: 32F) generalized tonic-clonic seizure; (case 4: 67F)) confusion and disorientation, (case 5: 27F) progressive headache, tinnitus, nausea and blurring of vision. All patients had low complement 3 (C3) levels and were treated with steroids, and sent home improved. The challenge of discriminating the varied clinical manifestations to the possibility of underlying CNS infections were heightened by the financial limitations of necessary diagnostics needed to identify the underlying causes. CONCLUSION: Good clinical skills and appropriate diagnostics and laboratories played an important role in the five cases presented creating a clearer clinical picture and in ruling out secondary causes thus directly channeling the management in these cases.

Association of Neutrophil-to-Lymphocyte Ratio (NLR) and Platelet-to-Lymphocyte Ratio (PLR) to disease activity in Filipino lupus patients

Background@#Systemic lupus erythematosus (SLE) is a chronic, multisystem, autoimmune disease characterized by autoantibody production, immune complex deposition and excessive pro-infl ammatory cytokine production due to an aberrant and dysfunctional immune system. Disease activity markers for SLE are helpful in the management and prognostication of the disease. The neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) have been studied as a novel infl ammatory marker and prognostic markers for cardiovascular diseases, infl ammatory disorders and malignancies.@*Objective@#The aim of the study is to investigate the association of NLR and PLR to disease activity of Filipino patients with SLE.@*Methods@#This is a cross-sectional study done through a retrospective chart review of 135 Filipino SLE patients divided into two groups. Group 1 (SLEDAI-2K score of <3) had 64 patients who were in low disease activity/remission and group 2 (SLEDAI2K score of ≥3) had 71 patients who were in active disease. Clinical characteristics and disease activity parameters (C3, anti-dsDNA, ESR) and NLR and PLR were compared in the two groups. Correlations of NLR and PLR with established clinical and laboratory disease activity markers of SLE (C3, anti-dsDNA, SLEDAI-2K scores) were analyzed.@*Results@#The group 2 or those with active disease had signifi cantly higher NLR (2.947 ± 1.756 vs. 1.868 ± 0.832, p-value of <0.001) and PLR (205.9 ± 122.2 vs. 140.2 ± 53.0, p-value of <0.001) levels compared to group 1. NLR and PLR values were also signifi cantly higher in patients with lupus nephritis. NLR was positively correlated with anti-dsDNA (r = +0.490, p-value of <0.001) and SLEDAI-2K scores (r = +0.496, p-value of <0.001). NLR was negatively correlated with C3 (r = -0.336, p-value of <0.001). PLR was also positively correlated with anti-dsDNA (r = +0.301, p-value of <0.001) and SLEDAI-2K scores (r = +0.369, p-value <0.001). PLR was also negatively correlated with C3 levels (r = -0.215, p-value 0.012). Using the ROC curve analysis, the cut-off values in predicting active disease in SLE were 1.968 (sensitivity 77.5%, specifi city 75%) for NLR and 144.53 (sensitivity 63.4%, specifi city 60%) for PLR. The cut-off values in predicting lupus nephritis were 2.121 (sensitivity 73.1%, specifi city 60%) for NLR and 167.0 (sensitivity 65.4%, specifi city 68%) for PLR.@*Conclusions@#NLR and PLR were signifi cantly higher among Filipino SLE patients with active disease including lupus nephritis refl ecting active infl ammation. NLR and PLR correlated well with established disease activity markers for SLE namely C3, anti-dsDNA, and SLEDAI-2K scores. NLR and PLR could be a useful and convenient disease activity marker for SLE patients.

Tocilizumab for refractory adult-onset still’s disease: Report of three cases

OBJECTIVES@#To present three cases of adult-onset still’s disease (AOSD) who was initially refractory to corticosteroid therapy but were successfully treated with an interleukin-6 (IL-6) inhibitor, tocilizumab (TCZ). @*BACKGROUND@# Adult-onset Still’s Disease (AOSD) is a systemic inflammatory disorder of unknown etiology characterized by quotidian fever, evanescent rash, and arthritis/arthralgia. The pro-inflammatory cytokine interleukin (IL) – 6 has been implicated in its pathogenesis. @*CASE PRESENTATION@#Three patients (40F, 37F, and 27M) presented with quotidian fever, evanescent maculopapular rash, arthritis, anemia, leukocytosis, elevated acute phase reactants and hyperferritinemia of 3 to 4 months duration. All were diagnosed AOSD by Yamaguchi criteria after extensive work up to exclude other diagnostic possibilities. Each patient received high dose corticosteroids and 2 patients also received methotrexate (MTX) with initial improvement of symptoms. However, there was recurrence and exacerbation of clinical symptoms on tapering of steroid doses. Each patient was then given TCZ at 8 mg/kg. Within a month of the initial dose of TCZ, there was dramatic clinical and laboratory improvement, enabling rapid steroid dose tapering. @*CONCLUSION@#This series substantiates the role of IL-6 in the pathomechanisms of AOSD and demonstrates use of TCZ in the management of AOSD refractory to corticosteroids.

Interstitial lung disease and pulmonary arterial hypertension in overlap syndrome: A case report

OBJECTIVE@#To present the onset of severe pulmonary arterial hypertension (PAH) in a patient with interstitial lung disease (ILD) associated with overlap syndrome.@*CASE PRESENTATION @#A 42-year-old female was diagnosed with overlap syndrome consisting of systemic lupus erythematosus (SLE), systemic sclerosis (SSc) and rheumatoid arthritis (RA). The serologic profi le included positive antinuclear antibody (ANA), anti-dsDNA, anti-RNP, anti-Ro, anti-Scl70, anti-Sm, rheumatoid factor and hypocomplementemia (C3, C4). She had chronic stable ILD for 17 years maintained on hydroxychloroquine (HCQ), prednisone 5 mg/day and indacaterol. The current admission was due to progressive dyspnea and right-sided heart failure over the past month. Chest radiograph showed pulmonary congestion, and 2-dimensional echocardiography (2DE) disclosed severe PAH with systolic pulmonary arterial pressure (SPAP) of 76 mmHg by tricuspid regurgitation (TR) jet, dilated right ventricle (RV) with poor systolic function, moderate pericardial effusion with no signs of tamponade. She received furosemide, beraprost, sildenafi l, and prednisone was increased to 20 mg/ day. Two weeks following discharge, there was complete resolution of symptoms and repeat 2DE showed non-dilated RV with good systolic function, normal SPAP of 21.4 mmHg and minimal pericardial effusion. Prednisone was tapered to 5 mg/day; beraprost, sildenafi l and HCQ were continued.@*CONCLUSION@#Overlap syndrome was diagnosed by the combination of clinical features and serology distinctive of SLE, SSc and RA. Her illness, particularly ILD, was adequately controlled over several years, until the recent onset of PAH complicated by right-sided heart failure. The dramatic response to high-dose steroids is more consistent with infl ammatory vasculitis of SLE activity rather than fi brosis typical of SSc.

Gastrointestinal Vasculitis in Systemic Lupus Erythematosus: A successful treatment with Belimumab

Introduction@#Gastrointestinal (GI) vasculitis among systemic lupus erythematosus (SLE) patients is a rare manifestation confounded with non-specific clinical symptoms and laboratory parameters which delay diagnosis leading to increase morbidity and mortality. This is a case report of a patient with of GI vasculitis who was successfully treated with belimumab@*Case presentation@#We describe a case of a Chinese descent, 24-year-old female who was diagnosed with SLE presenting as malar rash, arthritis, intermittent fever, positive antinuclear antibody (ANA), high titer anti double-stranded DNA and low serum complement. She had gastrointestinal manifestations of colicky abdominal pain, vomiting and diarrhea, with computed tomography scan findings of diffuse mucosal edema involving both small and large intestines, with “target” sign strongly suggestive of GI vasculitis. She initially showed good response to methylprednisolone pulse therapy, but with recurrence of abdominal pain after three months. Repeat abdominal CT showed perforated viscus at the ileal segment with pneumoperitoneum, requiring emergency exploratory laparotomy and colostomy placement. Subsequent clinical course was marked by intolerance to oral steroid requiring regular administration of high dose intravenous steroids. Belimumab was started months after surgery and maintained for two years now. She was successfully shifted to oral prednisone, tapered to lowest dose and underwent uneventful intestinal reanastomosis with closure of colostomy.@*Discussion@#Gastrointestinal (GI) vasculitis is one of the most serious gastrointestinal complications SLE presenting as acute abdominal pain. Our patient was diagnosed based on abdominal CT scan which led to an accurate diagnosis and prompt treatment. Supportive measures, surgery, and belimumab impacted the outcome of this patient.@*Conclusion@#Gastrointestinal (GI) vasculitis in SLE has a good outcome with early diagnosis and intervention. Our patient responded well with surgery, steroid and belimumab, a fully human recombinant immunoglobulin G (IgG) 1λ monoclonal antibody. This case report showed that belimumab is a good alternative treatment for lupus GI vasculitis.

Lupus among Filipinos: Unmet needs

@#Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with a wide range of manifestations and potential to affect several organ systems. Complications arise from the disease itself as well as the medications especially glucocorticoids, significantly contributing to overall morbidity and mortality. SLE predominantly affects patients during prime productive years resulting in a substantial economic burden on the patient, caregivers, and society due to direct, indirect and intangible costs. The University of Santo Tomas (UST) lupus database established in 2008 and supported by Lupus Inspired Advocacy (LUISA), aims to bring recognition of SLE as an important disease among Filipinos, serving as the impetus to drive policy makers to include SLE in the national health agenda.

Severe Keratoderma Blenorrhagicum simulating Psoriasis in reactive Arthritis: A case report

Introduction@#Severe keratoderma blenorrhagicum (KB) is a rare cutaneous manifestation of reactive arthritis (ReA) which can be indistinguishable from psoriasis, making the diagnosis challenging. This is a case of reactive arthritis in a 33-year-old female presenting with disabling, painful oligoarthritis which was accompanied by generalized pustular and scaly rashes simulating psoriasis.@*Case@#A 33-year-old female, Filipino, single with no known co-morbidities presented with disabling, painful oligoarthritis which was accompanied by generalized pustular and scaly rashes of two weeks duration. Her symptoms were preceded a few days earlier with a transient episode of conjunctivitis. She also reported having recently received treatment for “urinary tract infection”. There were generalized hyperkeratotic papules with areas of desquamation overlying erythematous skin involving the scalp, hairline, trunk, and extremities including palms and soles, with onycholysis on all digits. The right wrist and both ankles were warm, swollen and tender, with dactylitis involving most toes. Dermatology consult concurred with the diagnosis of keratoderma blenorrhagicum associated with reactive arthritis, over psoriasis or psoriatic arthritis, and she was started on prednisone 60 mg/day; methotrexate (MTX) 20 mg/week and folic acid were added a week later. With dramatic resolution of both skin and joint involvement, prednisone was tapered to 10 mg/day over the next three weeks and MTX was maintained at 15 mg/week, with no rebound nor recurrence of symptoms.@*Conclusion@#Severe KB is a rare cutaneous manifestation of ReA which can be indistinguishable from psoriasis. The acute onset of symptoms, recent history of eye inflammation and genitourinary tract infection strongly favored ReA over psoriasis. A further hallmark of KB is the presence of sterile pustules on the palms and soles. Histologically, KB has more numerous pustules and massive hyperkeratosis compared to psoriasis. Moreover, the dramatic response to systemic steroids, without rebound nor recurrence upon steroid taper or discontinuation favors KB over psoriasis.

Hospitalizations, renal activity and damage incur the highest medical costs among Filipino patients with Systemic Lupus Erythematosus

Introduction@#Systemic lupus erythematosus (SLE) predominantly affects individuals at peak age of productivity, and medical costs negatively impact on personal, family and community resources. This study aimed to identify annual medical costs and cost predictors among Filipino SLE patients.@*Methods@#Direct annual healthcare costs were determined by survey questionnaires conducted among patients aged > 18 years with minimum one-year illness duration, consecutively seen at the lupus clinics of University of Santo Tomas (UST) Hospital from February to July 2016. Excluded were costs related to biologics. Predictors of cost were estimated using multiple regression analysis.@*Results@#Respondents included 300 SLE patients, 270 females, (94%) age range 11-62 years, mean age 32.84±9.89 at SLE diagnosis, mean disease duration 5.87±5.58 (1-36) years. Median and mean annual direct medical cost was Php 90,950 and Php 133,040 respectively (range Php 17,440859,050). Annual cost was higher in those requiring dialysis (n=16) compared to those not requiring dialysis (n=150) vs those without nephritis (n=134), (median Php 595,400 vs 144,700 vs 55,020 respectively), p<0.001. End stage renal disease (ESRD) (p<0.001), mycophenolate use (p<0.001), high frequency of clinic visits (p=0.016) and lupus-related hospitalizations (p=0.018) were independent variables which significantly contributed to annual costs.@*Conclusion@#Nephritis especially if requiring dialysis was the most important cost predictor in this cohort, increasing annual costs to seven-fold. Mycophenolate use, lupusrelated hospitalizations and clinic visits increased annual costs by 147.2%, 173.8% and 2.6% respectively. This study reinforces the need for early recognition and aggressive disease control to prevent complications especially in those with renal involvement.