A case series of pulmonary alveolar proteinosis: Response differently to whole lung lavage.

Pulmonary alveolar proteinosis (PAP) is a rare disease and its prognosis can be improved by whole lung lavage (WLL). Herein, we present three cases with idiopathic PAP treated successfully with either single or double WLL in the same setting. All three of them presented with exertional dyspnoea with radiographic findings of pulmonary infiltrates. They showed a marked clinical and physiologic improvement post WLL. Two of them were in remission. These three cases were diagnosed using different lung biopsy modalities, including video-assisted thoracoscopic lung biopsy, computed tomography-guided percutaneous transthoracic tru-cut needle lung biopsy, and transbronchial forceps lung biopsy (TBLB), respectively. The current cases have shown that TBLB may provide adequate diagnostic yield, and the invasive surgical lung biopsy may not be necessary to achieve a definitive diagnosis.

Diagnostic performance of anti-RA33 antibody as a serological marker for rheumatoid arthritis.

INTRODUCTION: Rheumatoid arthritis is diagnosed based on the 2010 Rheumatoid Arthritis Classification Criteria whereby rheumatoid factor and anti-citrullinated protein antibody are the serological markers included in these criteria. Anti-RA33 antibody has the potential to provide additional diagnostic value in rheumatoid arthritis. The aim of this study is to determine the diagnostic performance of anti-RA33 antibody as a serological marker for rheumatoid arthritis. MATERIAL AND METHODS: Thirtyfour patients with rheumatoid arthritis and 34 non-rheumatoid arthritis individuals were included in this cross-sectional study. Anti-RA33 antibody and rheumatoid factor were performed on all samples. RESULTS: The sensitivity, specificity, positive and negative predictive value for anti-RA33 antibody and rheumatoid factor were 41.1%, 97.1%, 93.3%, 62.3% and 64.7%, 79.4%, 75.9%, 69.2% respectively. The overall sensitivity and specificity if either anti-RA33 antibody or rheumatoid factor are positive were 79.4% and 76.47% respectively. CONCLUSION: Anti-RA33 antibody showed good specificity and positive predictive value and could be considered as a potential serological marker for rheumatoid arthritis diagnosis.

Suicidal ideation in systemic lupus erythematosus: NR2A gene polymorphism, clinical and psychosocial factors.

Background Systemic lupus erythematosus (SLE) patients are a high-risk population for suicide. Glutamatergic neurosystem genes have been implicated in the neurobiology of depression in SLE and suicidal behaviour in general. However, the role of glutamate receptor gene polymorphisms in suicidal behaviour among SLE patients remains unclear in the context of established clinical and psychosocial factors. We aimed to investigate the association of NR2A gene polymorphism with suicidal ideation in SLE while accounting for the interaction between clinical and psychosocial factors. Methods A total of 130 SLE patients were assessed for mood disorders (MINI International Neuropsychiatric Interview), severity of depression (Patient Health Questionnaire-9), suicidal behaviour (Columbia-Suicide Severity Rating Scale), socio-occupational functioning (Work and Social Adjustment Scale), recent life events (Social Readjustment Rating Scale) and lupus disease activity (SELENA-SLE Disease Activity Index). Eighty-six out of the 130 study participants consented for NR2A genotyping. Results Multivariable logistic regression showed nominal significance for the interaction effect between the NR2A rs2072450 AC genotype and higher severity of socio-occupational impairment with lifetime suicidal ideation in SLE patients ( p = 0.038, odds ratio = 1.364, 95% confidence interval = 1.018-1.827). However, only the association between lifetime mood disorder and lifetime suicidal ideation remained significant after Bonferroni correction ( p < 0.001, odds ratio = 33.834, 95% confidence interval = 7.624-150.138). Conclusions Lifetime mood disorder emerged as a more significant factor for suicidal ideation in SLE compared with NR2A gene polymorphism main and interaction effects. Clinical implications include identification and treatment of mood disorders as an early intervention for suicidal behaviour in SLE. More adequately-powered gene-environment interaction studies are required in the future to clarify the role of glutamate receptor gene polymorphisms in the risk stratification of suicidal behaviour among SLE patients.

The association between serum prolactin levels and interleukin-6 and systemic lupus erythematosus activity.

Based on the recent evidence of association between hyperprolactinemia and systemic lupus erythematosus disease activity (SLEDAI), a study was conducted to analyze the association of hyperprolactinemia with lupus nephritis disease activity. In this cross-sectional study, the analysis was conducted on SLE patients who visited the University Kebangsaan Malaysia Medical Centre (UKMMC) Nephrology Clinic from August 2015 till February 2016. The disease activity was measured using the SLEDAI score, with more than 4 indicating active lupus nephritis. Basal resting prolactin level was analyzed in 43 patients with lupus nephritis, in 27.9% of them had raised serum prolactin. The median of serum prolactin level at 0 minutes was 19.91 ng/mL (IQR: 15.95-22.65 ng/ mL) for active lupus nephritis, which was significantly higher compared to the median of serum prolactin level of 14.34 ng/mL (IQR: 11.09-18.70 ng/mL) for patients in remission (p=0.014). The serum prolactin level positively correlated with SLEDAI (rhos: 0.449, p=0.003) and the UPCI level in lupus nephritis patients (rhos: 0.241, p=0.032). The results were reproduced when the serum prolactin was repeated after 30 minutes. However, the serum prolactin levels at 0 minutes were higher than those taken after 30 minutes (p=0.001). An assessment of serum IL-6 levels found that the active lupus nephritis patients had a higher median level of 65.91 pg/ mL (IQR: 21.96-146.14 pg/mL) compared to the in-remission level of 15.84 pg/mL (IQR: 8.38-92.84 pg/mL), (p=0.039). Further correlation analysis revealed that there was no statistical correlation between the interleukin (IL)-6 levels with serum prolactin, SLEDAI and other lupus nephritis parameters. An ROC curve analysis of serum prolactin at 0 minutes and serum prolactin after 30 minutes and IL-6 levels for prediction of SLE disease activity provided the cutoff value of serum prolactin at 0 minutes, which was 14.63 ng/mL with a sensitivity of 91.7% and specificity of 58.1% and AUC of 0.74 (p=0.015). This study concurred with the previous findings that stated that hyperprolactinemia is prevalent in SLE patients and correlated with clinical disease activity and UPCI level. The baseline of the fasting serum prolactin level was found to be a sensitive biomarker for the evaluation of lupus nephritis disease activity.

Implications of immunosuppressive agents in cardiovascular risks and carotid intima media thickness among lupus nephritis patients.

INTRODUCTION: Patients with systemic lupus erythematosus, particularly with lupus nephritis (LN), are at risk of premature cardiovascular (CV) disease. OBJECTIVE: To determine the association between immunosuppressive medications, traditional CV risk factors and carotid intima media thickness (CIMT) among patients with LN. METHODOLOGY: This was a cross-sectional study in which consecutive LN patients attending the Nephrology/SLE Clinic were evaluated for traditional CV risk factors. Detailed information on their treatment was obtained from their medical records. CIMT, an excellent marker of subclinical atherosclerosis, was measured by B Mode carotid ultrasound. RESULTS: A total of 82 patients with LN with a mean age of 33.9 ± 9.8( )years were recruited. More than half had hypertension (n = 55, 67.1%) and dyslipidemia (n = 43, 52.4%) as traditional CV risks. Longer history and higher cumulative dose of corticosteroids were associated with hypertension, but use of intravenous methylprednisolone was associated with lower systolic and diastolic blood pressure and lower serum total cholesterol and triglyceride levels (p < 0.05 each). Hydroxychloroquine use was associated with lower total serum cholesterol and serum low-density lipoprotein levels (p < 0.05). Although the use of cyclosporine A (CyA) was associated with hypertension (p < 0.05), those who received a lower cumulative dose of CyA had thicker CIMT (r (s) = -0.33, p =0.01) and CyA use remained an independent predictor of CIMT during linear regression analysis. There were no associations between CIMT and cumulative dose and duration of steroids, hydroxychloroquine, azathioprine, mycophenolic acid and cyclophosphamide. CONCLUSION: Aggressive treatment of severe LN and the use of CyA as a steroid-sparing agent may have protective effects against premature atherosclerosis.

Beyond the joints in rheumatoid arthritis: Effects of adalimumab on hematologic and lipid indices.

Tumor necrosis factor alpha (TNFα) is a multifunctional cytokine which plays a pivotal role in the pathogenesis of rheumatoid arthritis (RA). Apart from its well recognized proinflammatory properties, it is known to interfere with lipid metabolism and erythropoiesis. We evaluated the effects of adalimumab on hematologic, lipid and inflammatory parameters using data from patients on adalimumab 40 mg fortnightly from 2 centers in Malaysia. Mean changes in laboratory values from baseline to Weeks 4, 12 and 24 were compared using paired T test and Wilcoxon signed-rank test. We studied 18 patients with RA who were on adalimumab 40 mg fortnightly. The inflammatory markers i.e. erythrocyte sedimentation rate and C reactive protein showed significant changes as early as at week 4 compared to baseline with p values of 0.003 and 0.005, respectively. From a baseline of high disease activity with a mean Disease Activity Score using 28 joint counts (DAS 28) of 5.3, there was a steady improvement in the disease activity and remission was achieved at week 24 with a DAS 28 of 2.4. The hemoglobin level improved at week 12 (p=0.013) and this was sustained till week 24. As opposed to previous studies, the LDL level significantly decreased at week 12 (p=0.015) and this change persisted till week 24 (p=0.001). The total cholesterol showed a similar pattern as the LDL. The pharmacodynamics of adalimumab therapy in rheumatoid arthritis extend beyond the joints with favorable effects on haemoglobin and lipid profile.