Association of New Generation Anti-CCP Antibodies with Disease Severity and Functional Status in Rheumatoid Arthritis Patients

@#Introduction: Detection of anti-cyclic citrullinated peptide (anti-CCP) antibodies in patients with rheumatoid arthritis (RA) is associated with higher disease activity and lower functional ability. This study investigated the presence of the new generation of anti-CCP antibodies (anti-CCP2 IgG, anti-CCP2 IgA and anti-CCP3.1 IgG/IgA) and their association with disease severity and functional status of RA patients. Methods: A total of 46 RA patients and 40 healthy controls participated in this cross-sectional study that was conducted at the Rheumatology Clinic, Hospital Universiti Sains Malaysia. Blood samples were taken from all participants for anti-CCP2 IgG, anti-CCP2 IgA, and anti-CCP3.1 IgG/IgA analysis. Disease severity and functional status of RA patients were measured using the Disease Activity Score-28 (DAS28) and the modified Health Assessment Questionnaire (mHAQ) respectively. Results: Significantly higher proportion of RA patients were found with positive anti-CCP2 IgG (63.0%), anti-CCP2 IgA (37.0%), and anti-CCP3.1 IgG/IgA antibodies (63.0%) than the healthy controls. No significant association was found between anti-CCP antibodies status and mean DAS28 score of the RA patients. However, RA patients with negative anti-CCP2 IgG status had higher mean mHAQ score than patients with positive anti-CCP2 IgG status. Conclusion: Our study has demonstrated detection of the new generation anti-CCP antibodies in RA patients, supporting the use of autoantibodies in RA diagnosis. While no significant association was found between the presence of anti-CCP antibodies and disease severity of RA patients, the absence of anti-CCP2 IgG was associated with worse function and greater disability of the patients.

Undiagnosed Takayasu Arteritis in Pregnancy

@#Takayasu arteritis is a chronic inflammation involving large vessels and it often occurs in young women of childbearing age. We described a case of a 29- year- old lady with previous history of proliferative ischemic retinopathy was noted to have low upper limbs blood pressure and weak upper limb pulses postpartumly. An urgent CT angiogram of thorax revealed features suggestive of large vessel vasculitis with involvement of ascending arch, descending aorta and its main branches, corresponding to type II TA . She was diagnosed to have Takayasu arteritis post delivery, and she underwent a successful pregnancy without intrapartum and postpartum complications. High index of suspicion must be given for pregnant patient who have persistent low blood pressure and weak pulse for early detection to avoid severe complications.

Sjogren’s Syndrome with Interstitial Lung Disease

@#Sjogren’s syndrome (SS) is an autoimmune disease affecting exocrine glands with known properties to cause chronic systemic multi-organ disease involvement. It produced the typical features of sicca syndrome, but due to insidious onset of the disease, patient may present with complications of the condition at the initial presentation. We present a case of primary Sjogren’s syndrome (SS) who first presented with pulmonary manifestations and was subsequently diagnosed as Lymphocytic Interstitial Pneumonia (LIP). The patient was extensively investigated and received appropriate treatment modalities.

Vitamin D Levels and Steroid Usage are not Associated with Disease Activity in Systemic Lupus Erythematosus Patients

@#Introduction: Suboptimal vitamin D levels are commonly presented by systemic lupus erythemathosus (SLE) patients. This is likely due to protection measures from sunshine exposure adopted by SLE patients to reduce the likelihood of SLE flares onset. In this study, we investigated the vitamin D level among SLE patients and its association with SLE Disease Activity (SLEDAI) scores and among groups of steroid and non-steroid usage. Methods: We recruited 84 SLE patients who attended the Rheumatology Clinic of Hospital Universiti Sains Malaysia from June 2018 until October 2018. Their clinico-demographic data were retrieved and serum vitamin D immunoassay was conducted to measure the vitamin D levels of each patient Vitamin D levels were categorized as normal (≥75nmol/L), insufficient (50-74 nmol/L) or deficient (<50 nmol/L). Comparison between the clinico-demographic parameters with vitamin D levels were conducted using the Fisher’s exact test (for categorical variables) and unpaired t-test (for continuous variables). Results: The mean vitamin D level among the subjects was 40.79 ± 20.2 nmol/L. Fifty-eight (69%) patients were vitamin D deficient, while 20 (23.8%) patients were vitamin D insufficient, and only 6 (7.1%) patients had sufficient level of vitamin D. Vitamin D status was not significantly associated with SLEDAI score (p=0.185) as well as between steroids and non-steroids groups (p=0.255). Conclusion: Vitamin D deficiency occurred in majority of our SLE patients. SLE disease activities were not associated with the status of vitamin D or steroid usage.

Severe Pulmonary Tuberculosis With Organizing Pneumonia: A Diagnostic Ambiguity

@#Pulmonary TB may present insidiously and ambiguously, leaving clinicians with a diagnostic dilemma. A 30-year-old lady with underlying spinocerebellar ataxia presented with progressive shortness of breath, prolonged cough with whitish sputum, loss of appetite and weight loss of 1-year duration. Physical examination showed a cachectic, tachypnoeic female with finger clubbing and coarse crepitations on lung auscultation. Chest radiograph showed bilateral air space opacities relatively sparing the upper zone. Contrast-enhanced CT thorax revealed bilateral cavitary necrotising consolidations, multiple scattered lung nodules with surrounding ground-glass opacities. After exclusion of alternative diagnoses, cryptogenic organizing pneumonia diagnosis was made. She had a rapid clinic improvement once steroid was started. TB polymerase chain reaction (PCR) from bronchoscopic bronchial washing eventually was positive. Anti-TB treatment was started, and oral steroid was slowly tapered down. Organizing pneumonia (OP) may complicate pulmonary TB. Diagnosing OP without lung biopsy requires a multi-disciplinary approach, taking into consideration all available evidences. Early steroid therapy is lifesaving and should be considered after thorough exclusion of alternative diseases.

A boy with peri-oral lesion

@#A 4-year-old boy complained of dryness of lips for a 3-month duration. The dryness progressed to becoming scaly and painful, and lesions extended beyond the lip area. The condition was associated with peri-oral itchiness. The boy was observed to be licking his lips subconsciously a few times per minute. The lesions started with a habitual licking of the lips. There was no history of allergies or any recent intake of a new drug. There was also no history of atopy in the patient or his family

A 15-year single centre retrospective study of antiphospholipid syndrome patients from Northern Malaysia

Background: Antiphospholipid syndrome (APS) is an autoimmune disorder characterised by thrombosis and/or pregnancy morbidity in the presence of antiphospholipid antibodies (aPLs) based on the Sydney criteria. We aimed to explore the clinico-laboratory features and treatment strategies of APS patients retrospectively. Methodology: The medical records of APS patients registered under Hospital Universiti Sains Malaysia (Kelantan state) between 2000 and 2015 were reviewed. Results: A total of 17 APS subjects (age 40.7 ± 12.8 years) including 11 primary (64.7%) and six secondary APS (35.3%) patients were identified. The follow-up period was 9.5 ± 6.7 years with male:female ratio of 1.0:4.7. Pregnancy morbidity was the most common clinical manifestation (11/14; 78.6%) followed by recurrent venous thrombosis (10/17; 58.8%). For other clinical features, menorrhagia was the most frequently observed manifestation (4/14; 28.6%) followed by aPLs-associated thrombocytopenia (4/17; 23.5%) and ovarian cyst (3/14; 21.4%). LA and aCL were positive in 94.1% (16/17) and 81.8% (9/11) of the patients, respectively. APTT value (76.7 ± 17.0 sec) was significantly high (p < 0.05). Low intensity warfarin alone was successful to maintain target INR (2.0 - 3.0) and prevent recurrence of thrombosis. Conclusion: The tendency of pregnancy morbidity in this cohort of Malaysian Kelantanese APS patients was high compared to other previously reported APS cohorts. Low intensity warfarin was successful in preventing recurrence of thrombosis, however, APS women receiving long-term anticoagulants should be monitored for possible occurrence of menorrhagia and ovarian cysts.

Serum Vascular Endothelial Growth Factor (VEGF) as a Biomarker for Disease Activity in Lupus Nephritis

Background: Previous studies have shown that serum VEGF levels were elevated in patients with active systemic lupus erythematosus (SLE), especially in those with lupus nephritis (LN). In this case control study, we aimed to compare serum levels of VEGF in SLE patients between LN, non-LN and healthy participants to determine the association between serum VEGF levels and the activity and histological classes of lupus nephritis. Methods: Blood samples were obtained from 92 SLE patients (46 LN and 46 non-LN) and 26 controls. Data were collected from medical records. Serum VEGF assays were performed by specific, enzyme-linked immunosorbent assay kits (ELISA). Laboratory investigations included urinalysis, urine protein–creatinine ratio, serum creatinine, albumin and VEGF levels. Blood pressure, renal biopsy result and treatment were recorded. LN activity was evaluated using the renal subscale of the British Isles Lupus Assessment Group (rBILAG, 2004). The rBILAG measures blood pressure (diastolic and systolic), urine protein, serum creatinine, calculated glomerular filtration rate (GFR), presence of active urinary sediments and histological evidence of active nephritis. Results: Serum VEGF was elevated in SLE patients with LN compared with the non-LN group and healthy controls. The levels found were significantly higher in the sera of patients with active nephritis compared to those with quiescent nephritis (P = 0.024). The study did not find a statistically significant relationship between serum VEGF levels and histological classes of LN. Conclusion: There was no significant difference of serum VEGF level between LN and non-LN SLE groups and between the non-LN group and healthy controls. However, there were increased levels of serum VEGF in the LN group, especially in patients with active nephritis as compared to quiescent nephritis group. This reflects the role of VEGF in the pathogenesis of lupus nephritis, however the clinical potential of this biomarker needs further study.

Correlation of Demographic and Clinical Characteristics with Rheumatoid Factor Seropositivity in Rheumatoid Arthritis Patients

Background: The rheumatoid factor (RF) blood test is the most commonly adopted test for the diagnosis of rheumatoid arthritis (RA). RA patients who are seropositive for RF might face a greater likelihood of developing more aggressive symptoms. Methods: Our goal was to study the demographic and clinical characteristics, as well as their correlation with RF seropositivity, among a series of 80 RA patients aged ≥ 18 years who attend Hospital Universiti Sains Malaysia (HUSM). Results: Of the 80 RA patients included in this study, 66 (82.5%) were female and 14 (17.5%) were male. No significant associations between RF seropositivity and demographic and/ or clinical characteristics or other laboratory investigations were observed, including gender, morning stiffness, individual joint involvement (from multiple sites of the body), and erythrocyte sedimentation rate (ESR) measurement. However, a significant association between RF seropositivity and patients aged ≥ 50 was found (P = 0.032). Conclusion: RF seropositivity was found to be more common in much older RA patients.

Evaluation of Endothelial Cell Adhesion Molecules and Anti-C1q Antibody in Discriminating between Active and Non-Active Systemic Lupus Erythematosus

Background : Detecting the active state of systemic lupus erythematosus (SLE) is important but challenging. This study aimed to determine the diagnostic accuracy of serum endothelial cell adhesion molecules (ICAM-1 and VCAM-1) and anti-C1q antibody in discriminating between active and non-active SLE. Methods: Using SELENA-SLE disease activity index (SLEDAI), 95 SLE patients (45 active and 50 non-active) were assessed. A score above five was considered indicative of active SLE. The blood samples were tested for serum ICAM-1, VCAM-1 and anti-C1q antibody using enzyme-linked immunosorbent assay (ELISA). Results: The levels of serum VCAM-1 and anti-C1q antibody were significantly higher in active SLE patients. Both VCAM-1 and anti-C1q were able to discriminate between active and non-active SLE ( p -value < 0.001 and 0.005, respectively). From the receiver operating characteristic curves (ROCs) constructed, the optimal cut-off values for VCAM-1 and anti-C1q antibody in discriminating between active and non-active SLE were 30.5 ng/mL (69.0% sensitivity, 60.0% specificity, PPV 58.5%, NPV 66.7%) and 7.86 U/mL (75.6% sensitivity, 80% specificity, PPV 77.3%, NPV 78.4%), respectively. However, serum ICAM-1 level was unable to discriminate between the two groups ( p -value = 0.193). Conclusion: Anti-C1q antibody demonstrated the best diagnostic accuracy in discriminating between active and non-active SLE patients