New therapies for systemic lupus erythematosus are rare. This is because of the complexity of the disease and its varied presentations. There are many variables and a variety of measurement scales that must be satisfied before a new agent is approved for use in humans. Attempts are ongoing to develop biological treatments for the disease using three approaches: B cell modulation, T cell regulation and cytokine inhibition. This paper reviews the current state of these three critical areas.

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Pulmonary hypertension (PH) is an important cause of morbidity and mortality in connective tissue diseases (CTDs). CTDs may cause PH due to several mechanisms; pulmonary arterial hypertension, associated interstitial lung disease, neuromuscular disease, and/or sleep disordered breathing leading to hypoxia, associated thromboembolic PH, and pulmonary venous hypertension due to left ventricular dysfunction. PH can be measured on echocardiography, but the gold standard for diagnosis is right heart catheterization. PH-specific therapy in addition to immunosuppression is the most common treatment used though data are scant. In this narrative review, we discuss the epidemiologic burden, clinical presentation, evaluation, and management of PH in CTDs.

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Background: Ultrasound (US) including power Doppler (PD) are increasingly being used to evaluate joint involvement in rheumatoid arthritis (RA). Aim of this study was to evaluate joint involvement in RA by US including PD and gray scale imaging and its comparison with conventional radiographic changes and correlation with disease activity parameters. Methods: Patients with RA of less than 3.5 years disease duration were subjected to detailed clinical examination and laboratory investigations. After X-ray imaging (posterior-anterior view) of both hand joints, PD and gray scale US examination of 14 joints of both hands was performed and mean cumulative flow signal score (CFS) was calculated. Disease activity score (DAS28) was also calculated for each patient. Results: Out of total 57 patients evaluated, 54 had abnormal findings on US as compared to only 17 having radiographic abnormalities. US could detect erosions in 29 patients including all of the fourteen patients who had radiographically detectable erosions. On US evaluation, radiocarpal joint was involved most frequently. The mean CFS was 1.17 ± 1.64 in patients who were in remission (DAS28 <2.6), 3.00 ± 3.46 in patients having low disease activity (DAS28 2.6–3.2), 5.25 ± 4.22 in patients with moderate disease activity (DAS28 3.2–5.1), and 6.95 ± 3.84 in patients with high disease activity (DAS28 > 5.1). The difference in CFS among these groups was statistically significant (P < 0.01). In 5 out of 12 patients with DAS28 <2.6, i.e., in remission, CFS were high showing subclinical synovitis. Mean CFS correlated significantly with DAS28 (r = +0.42, P < 0.05); C-reactive protein (r = +0.50, P < 0.05); and erythrocyte sedimentation rate (r = +0.39, P < 0.05). Conclusions: US detected CFS which an indicator of ongoing inflammation in RA patients with clinical remission (DAS28 <2.6). US is more sensitive than conventional radiography for detection of erosions. CFS on PD had a significant correlation with markers of disease activity.

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Objective: Most of the patients with proliferative lupus nephritis (LN) have high titer of anti-dsDNA antibody and low complement levels. In this study, we tried to predict proliferative LN with serological profile. Methods: This prospective study was conducted in fifty pateints with known systemic lupus erythematosus (SLE) with laboratory evidence of LN (proteinuria, microscopic hematuria, or increased serum creatinine). Serological profile (anti-dsDNA, C3, and C4) and renal biopsy were done in all patients. Results: Of 50 patients, 35 had Class IV (70%), 7 Class II (14%), 4 Class V (8%), and 4 had Class IV and V (8%) on renal biopsy. Totally, 39 (78%) patients had proliferative LN (Class IV and Class IV and V). The prevalence of anti-dsDNA, low C3, and low C4 was 97.1%, 68%, and 74% with LN and 97.4%, 84.6%, and 87.2% with proliferative LN (P < 0.001), respectively. About 72% (28 of 39 patients) with proliferative LN had the combination of anti-dsDNA positivity, low C3, and low C4 levels. However, whoever had the combination of anti-dsDNA positivity, low C3, and low C4 showed only proliferative LN on biopsy. Positive predictive value was 100% (P < 0.05). None of the patients with Class II or Class V (nonproliferative LN) had this combination of serology. Conclusion: In this study, it was found that proliferative LN can be predicted by serological profile alone. Thus it might be argued that immunosuppressive therapy (steroids and mycophenolate mofetil) may be started without renal biopsy in a known SLE patient with laboratory evidence of LN and positive serology; however, robust studies are required.

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Background: Novel treatments for osteoarthritis (OA) are needed for patients not responding to and/or not tolerating conventional treatments. In this prospective study the usefulness of Anakinra (Kineret) in the treatment of OA was evaluated. Methods: Eleven patients with symptomatic OA were treated with Anakinra (Kineret) over a 2–3 month period. Efficacy of response was determined if patients showed >30% improvement in the Western Ontario and McMaster Universities Osteoarthritis Index and/or Australian/Canadian Osteoarthritis Hand Index scoring with treatment. Nine of the 11 patients received Kineret intra-articular (IA) injections and 2/11 patients with erosive polyosteoarthritis received Kineret 100 mg subcutaneous injections daily for 30 days. Results: One of the two patients receiving systemic administration of Kineret showed mild efficacy. A total of 21 IA Kineret injections were performed on nine patients. Only 2/5 patients receiving IA Kineret injections into small/medium-sized joints showed efficacy and only 2/5 patients receiving IA Kineret injections into large joints (knees, shoulders) showed efficacy – but those patients showing efficacy with large joints injections had >50% improvement. Conclusion: In this study it was found that patients receiving large joint injections were more likely to show greater efficacy than those receiving small joint injections. Therefore, there seems to be a possible benefit of using Kineret (150–200 mg) in the treatment of OA in large joints and may represent an alternative to IA steroid in those patients in whom steroids may be contraindicated.

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Background: Major histocompatibility complex (MHC) or human leukocyte antigen (HLA) gene and some of the non-MHC genes are associated with genetic predisposition in rheumatoid arthritis (RA). The aim of the present study was to find the prevalence of HLA DRβ1 alleles and protein tyrosine phosphatase nonreceptor type 22 (PTPN22) gene single-nucleotide polymorphism (SNP) in RA patients and also assessed their correlation with laboratory and clinical parameters. Materials and Methods: One hundred and fifty cases of RA and 100 healthy controls were studied. relation to RA patients. HLA DRβ1 typing was done by low-resolution sequence-specific primer polymerase chain reaction and auto-antibodies (Abs) (rheumatoid factor [RF], anti-cyclic citrullinated peptide 2 (CCP2) Ab, anti-nuclear Ab, double-stranded deoxyribose nucleic acid, anticardiolipin Ab) were done by enzyme-linked immunosorbent assay. Results: In patients with RA, the most common HLA DRβ1 allele was DRβ1*04 (23.3%), followed by DRβ1*10 (20.7%), DRβ1*03 (9.3%), and DRβ1*01 (8.7%). Contrary to this, some alleles of DRβ1 were significantly less expressed in RA such as DRβ1*07 (P = 0.000) and DRβ1*14 (P = 0.010). DRβ1*04 positive patients had significantly more RF positivity while DRβ1*10 positive patients had increased RF and anti-CCP2 Ab. DRβ1*04 positive cases had positive correlation with disease activity score. DRβ1*10 positive patients had negative correlation with the age of the RA patients. These patients have shown early onset of disease. PTPN22 C1858T SNP was found in only 4% cases of RA. No correlation was established with PTPN22 SNP positivity and clinical parameters. Conclusion: In our study, RA patients have less DRβ1*04 positivity as compared to the Western literature. In our area, DRβ1*10 is more common than DRβ1*01. HLA DRβ1*07 and *14 are found to be protective for RA. PTPN22 SNP has not shown any diagnostic or prognostic significance while a follow-up study may be useful for prognostic importance of HLA DRβ1 typing in RA.

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Background: We evaluated the relationship between bone mineral density (BMD) and biomarkers of bone turnover in ankylosing spondylitis (AS) patients treated with anti-tumor necrosis factor alpha (TNF-α) agents. Methods: Fifty-one AS patients were screened, of which 27 were started on anti-TNF therapy in accordance to the assessment of AS guidelines. Detailed assessments of erythrocyte sedimentation ratio (ESR), Bath AS disease activity index (BASDAI), Bath AS functional index (BASFI), Bath AS metrological index (BASMI), AS disease activity score-ESR, and AS quality of life (AsQOL) questionnaire were done at baseline and 6 months. Vitamin D, parathyroid hormone, and osteocalcin were measured along with BMD of the lumbar spine, anteroposterior (AP) and lateral view, and hip. Results: Out of 27 patients, 12 patients had osteoporosis. At 6 months, significant improvements were seen for BASDAI (mean 2.33 ± 1.08, P < 0.01), BASFI (3 ± 1.31, P < 0.01), BASMI (3 ± 3.05,P = 0.019), and AsQOL (4 ± 3.02, P < 0.01) and these correlated with a decrease in ESR (15.6 ± 10.8,P = 0.01) at 6 months. The mean increase in BMD at the neck of femur, total hip, and lumbar AP view was 3.2% (P = 0.007), 3.1% (P = 0.004), and 2.5% (P < 0.001), respectively. The serum alkaline phosphatase level increased from a mean value of 190.3 ± 70.8 IU/ml at baseline to 225.4 ± 59.8 IU/ml, which was statistically significant at the 6-month follow-up (P = 0.006). The serum osteocalcin levels showed an increasing trend from a mean value of 2.32 ± 1.6 ng/ml at baseline to 3.32 ± 3.02 ng/ml at 6 months. Conclusion: Anti-TNF-α has a beneficial effect on bone metabolism resulting in improved bone formation.

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