Biologics Use in Asian Indian Patients with Ankylosing Spondylitis: A Physician's Perspective.

INTRODUCTION: Ankylosing Spondylitis (AS) with non-steroidal anti-inflammatory drug (NSAID) therapeutic failure is treated with biologics. AIM: To compare the clinical outcomes of different biologics for Asian Indian patients with AS who have NSAID therapeutic failure. MATERIALS AND METHODS: Thirty-five AS patients with NSAID failure were administered Etanercept (n=15) (50mg SQ, weekly) or Infliximab (n=20) (5mg/kg IV every 2(nd) month) based on patient convenience or physician discretion as per 2015 ACR/SAA/SPARTAN recommendations. Baseline demographic details, time to diagnosis, disease duration, presence of low backache, early morning stiffness, peripheral joint and extraarticular involvement, ESR, CRP values and HLA-B27 score were obtained. Baseline values of scores of BASMI-3 and MASES were calculated. To monitor the disease activity, BASDAI and ASDAS-ESR scores were recorded at baseline, and after 6 months and 12 months of therapy initiation. STATISTICAL ANALYSIS: Comparison of means: independent samples t-test; comparison of parameters over time: repeated measures ANOVA. RESULTS: Both groups were comparable in all parameters at therapy initiation except in the baseline BASMI-3 score which was significantly higher in patients who received Etanercept. Over 12 months of treatment, the reduction in disease activity, as evidenced by reduction in the mean BASDAI and ASDAS-ESR scores was statistically significant for all patients when considered together, as well as when Etanercept and Infliximab were considered separately (p<0.0001 in all cases). However, there was no statistically significant difference in the magnitude of reduction in the mean BASDAI and ASDAS-ESR scores between patients who received Etanercept and those who received infliximab (p=0.696 and 0.618 respectively). CONCLUSION: Etanercept and Infliximab offer statistically similar reduction in disease severity in Asian Indian AS patients with NSAID failure. Further studies with larger sample size are warranted.

Do IgA antibodies to Chlamydia trachomatis have protective role in humoral immunity: a study in reactive arthritis patients.

Chlamydia trachomatis-induced genitourinary Reactive Arthritis (ReA) can serve as good model for host-pathogen interaction. However, due to poor antigen presentation, cell-mediated immunity does not contribute as anticipated. Present study aims to evaluate protective role of anti-C. trachomatis antibodies vis-a-vis inflammatory chlamydial Major Outer Membrane Protein (MOMP). Prospective study was undertaken in 30 patients with genitourinary ReA. 30 Rheumatoid Arthritis (RA) and 30 osteoarthritis patients constituted controls. Subjects found to be PCR-positive for C. trachomatis were investigated for presence of MOMP in Synovial Fluid (SF) by fluorescence assay while anti-C. trachomatis IgA/IgM antibodies were estimated in SF/venous blood by ELISA. C. trachomatis MOMP was evident by the presence of elementary bodies in SF of 9 ReA PCR-positive patients (30%; p < 0.05 versus controls). Local secretory IgA antibodies were detected in 12 (40%) patients with ReA (p < 0.0001 versus controls); among 12 patients with anti-chlamydial IgA antibodies, 9 showed the presence of both MOMP and IgA antibodies in SF. 58.3% ReA patients (7/12) with secretory IgA antibodies were also positive for circulatory IgA antibodies (p < 0.01 versus controls). Serum IgM antibodies were present in 4 ReA (13.3%) and in 1 RA (3.3%) patient, respectively. In conclusion, the present study suggests that in ReA patients with chronic, persistent C. trachomatis infection in synovium, the chlamydial MOMP is triggering factor for generating a protective immune response by inducing anti-C. trachomatis IgA antibodies in the SF of large number of patients.

Successful autologous hematopoietic stem cell transplantation for a patient with rapidly progressive localized scleroderma.

Autologous hematopoietic stem cell transplant (HSCT) for rapidly progressive disease has not been reported in localized scleroderma. Our patient, a 16-year-old girl had an aggressive variant of localized scleroderma, mixed subtype (linear-generalized) with Parry Romberg syndrome, with no internal organ involvement, that was unresponsive to immunosuppressive therapy and was causing rapid disfigurement. She was administered autologous HSCT in June 2011 and has maintained drug-free remission with excellent functional status at almost 3.5 years of follow-up.

Diagnosis of Chlamydia trachomatis in patients with reactive arthritis and undifferentiated spondyloarthropathy.

INTRODUCTION: There is a paucity of information on the frequency of Chlamydia trachomatis-induced reactive arthritis (ReA) and undifferentiated spondyloarthropathy (uSpA) in India. In this study, arthritic patients suffering from ReA, uSpA, and rheumatoid arthritis (RA) were screened to investigate the presence of C. trachomatis infection in the synovial fluid (SF) or serum by molecular and non-molecular methods. METHODOLOGY: A total of 76 arthritic patients with ReA (n = 16) and uSpA (n = 22) composed the study group while those with RA (n = 38) served as controls. The detection of C. trachomatis DNA was done by semi-nested PCR (snPCR) and nested PCR (nPCR) targeting two different genes of C. trachomatis, namely major outer membrane protein and plasmid, respectively. The presence of serum or SF immunoglobulin IgG and IgA antibodies against C. trachomatis was studied by commercial enzyme-linked immunosorbent assay kits. RESULTS: The SF from 9 of 38 (23.6%) patients (5 with ReA and 4 with uSpA) was positive for at least one C. trachomatis DNA by snPCR or nPCR in comparison to RA (1/38 [2.6%]; p value < 0.05). There was no correlation between the snPCR or nPCR and the serological results of patients with ReA or uSpA. CONCLUSIONS: As molecular diagnostic techniques established intra-articular C. trachomatis infection among this group of seronegative spondyloarthropathies in India, these findings should be viewed with concern, and snPCR or nPCR should be considered for a more reliable diagnosis.

Identification of autoantibodies against transthyretin for the screening and diagnosis of rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic, autoimmune, systemic and inflammatory rheumatic disease that leads to inflammation of the joints and surrounding tissues. Identification of novel protein(s) associated with severity of RA is a prerequisite for better understanding of pathogenesis of this disease that may also have potential to serve as novel biomarkers in the diagnosis of RA. Present study was undertaken to compare the amount of autoantigens and autoantibodies in the plasma of RA patients in comparison to healthy controls. Plasma samples were collected from the patients suffering from RA, Osteoarthritis (OA), Systemic lupus erythematosus (SLE) and healthy volunteers. The screening of plasma proteins were carried out using 2-dimensional gel electrophoresis followed by identification of differentially expressed protein by MALDI-TOF MS/MS. Among several differentially expressed proteins, transthyretin (TTR) has been identified as one of the protein that showed significantly up regulated expression in the plasma of RA patients. The results were further validated by Western blot analysis and ELISA. In comparison to OA synovium, an exclusive significantly high expression of TTR in RA has been validated through IHC, Western blotting and IEM studies. Most importantly, the increase in expression of TTR with the progression of severity of RA condition has been observed. The autoantibodies against TTR present in the RA plasma were identified using immunoprecipitation-Western methods. The significant production of autoantibodies was validated by ELISA and Western blot analysis using recombinant pure protein of TTR. Hence, these novel observations on increase in TTR expression with the increase in severity of RA conditions and significant production of autoantibodies against TTR clearly suggest that a systematic studies on the role TTR in the pathogenesis of RA is immediately required and TTR may be used as a serum diagnostic marker together with other biochemical parameters and clinical symptoms for RA screening and diagnosis.

Clinical profile of benign joint hypermobility syndrome from a tertiary care military hospital in India.

BACKGROUND AND AIMS: Joint hypermobility when associated with symptoms in the absence of systemic rheumatologic disease is termed as benign joint hypermobility syndrome (BJHS). BJHS is often an under-recognised and a poorly managed entity. Indian studies on BJHS are very few and none have been carried out in any of the service rheumatology centres. Hence this retrospective study was carried out at a tertiary medical institute of the Indian Army to assess the varied clinical profile of BJHS. METHODS: All patients consecutively diagnosed as BJHS at the rheumatology clinic of the Army Hospital (Research and Referral) Delhi from May 2010 to May 2011 were included in the study. Their age, sex, presenting features, clinical profile, laboratory and radiological parameters were studied. RESULTS: The mean age of these patients was 30 ± 5.71 years with a median duration of symptoms of 42 (06-120) months. There were 45 males and 39 females (male : female = 1.15 : 1.00). The median Beighton's score in these patients was 6/9 (range 4-9). Most of our patients were military personnel (43/84), and all had knee joint pain with evidence of degenerative changes in 19 and synovitis in two patients. Eleven patients including nine military personnel had evidence of soft tissue rheumatism with associated fibromyalgia in four and anxiety disorder in one. Out of 18 patients with a Beighton's score of ≥ 7, nine had incidental findings of lateral head tilt on frontal observation. There was evidence of carpal tunnel syndrome in a patient with wrist synovitis and one patient had associated skin laxity without features of Ehlers-Danlos syndrome. CONCLUSION: BJHS is often under-recognized in clinical practice and is usually missed because of a lack of awareness. A high index of clinical suspicion to diagnose this entity is essential due to its associated morbidities, especially among those exposed to strenuous physical activities.

Nailfold capillaroscopy by digital microscope in an Indian population with systemic sclerosis.

AIM: Nailfold capillaroscopy (NFC) is a simple, non-invasive method with exceptional predictive value for the analysis of microvascular abnormalities, especially in systemic sclerosis (SSc) but remains underutilized due to cost factors of the nailfold videocapillaroscope, lack of expertise and availability issues. The aim of this study was to establish the utility of an inexpensive digital microscope to study NFC changes in SSc in correlation with disease subsets and extent of skin involvement. METHODS: Twenty-two diffuse cutaneous SSc (DSS), 20 limited cutaneous SSc (LSS) patients and 42 controls were evaluated with NFC using a digital microscope at 30× and 100× magnification. Digital micrographs were used to study qualitative and quantitative changes in microvasculature. RESULTS: The capillary density was significantly less in all cases of SSc as compared to controls (5.3 ± 1.4 vs. 8.7 ± 1.2; P < 0.00001). Disorganized architecture was much more prevalent in DSS versus LSS (86.4%vs. 25%). The vascular deletion score (VDS) was significantly higher in DSS as compared to LSS (P < 0.0001). Scleroderma pattern (SP) was seen in 18 (81.9%) and 15 (75%) of patients with DSS and LSS, respectively. Only 4% of normal subjects showed non-specific pattern and none showed SP. The mean modified Rodnan skin score (MRSS) was positively correlated with vascular deletion score (r = 0.572; P < 0.001) and negatively with capillary density (r = -0.8; P < 0.001). CONCLUSION: Nailfold capillaroscopy changes in SSc are related to disease subset and MRSS. NFC with digital microscope is a simplified, inexpensive, outpatient procedure with results comparable to previous studies.

Bone mineral density in young males with ankylosing spondylitis.

OBJECTIVE: To assess bone mineral density (BMD) abnormalities in young Indian males with ankylosing spondylitis (AS) and factors influencing this. METHODS: Eighty AS male subjects were compared with 160 age/sex matched controls for BMD of lumbar spine and proximal femur. AS subjects were evaluated and followed up every 3 months for disease activity. BMD was estimated at spine and proximal femur using the dual-energy X-ray absorptiometry (DXA) technique. RESULTS: All subjects were males with mean age of 32.9 ± 8.3 years and mean duration of disease was 8.1 ± 5.8 years. AS subjects had significantly lower BMD at the spine and femur as compared with controls (both P < 0.001). Using WHO standards, osteoporosis (OP) in spine and femur neck was seen in 28.75% (controls: 1.84%, P < 0.001) and 11.54% (controls: 1.23%, P < 0.001), respectively. No statistically significant difference in prevalence of OP was seen with disease duration, C-reactive protein levels and disease activity indices (all P > 0.05). Syndesmophytes were seen in 22.5% (n = 18) of AS subjects. There was no significant difference between BMD values at spine in AS subjects with or without syndesmophytes (0.91 + 0.16 g/cm(2) vs. 0.90 + 0.14 g/cm(2), P = 0.79). CONCLUSION: OP is a significant complication in AS even in young males with early disease, and more prevalent in the spine compared to femur. In our study, BMD was not influenced by disease activity indices, inflammatory markers or total disease duration. Spinal BMD is the most sensitive site for defining OP in AS.

Intramedullary fat necrosis, polyarthritis and panniculitis with pancreatic tumor: a case report.

Acute polyarthritis can occur in non-rheumatic systemic illnesses, presenting a diagnostic dilemma. We present an extremely rare case presenting as acute polyarthritis, panniculitis and medullary fat necrosis with underlying pancreatic pathology. This case report describes a young woman presenting with panniculits, pancreatic tumour, polyarthritis and intra-osseus fat necrosis with a fatal outcome. The medical fraternity needs to be aware of this potentially fatal albeit rare musculoskeletal complication secondary to a pancreatic pathology.

Bactericidal/permeability-increasing protein and cathepsin G are the major antigenic targets of antineutrophil cytoplasmic autoantibodies in systemic sclerosis.

OBJECTIVE: To study the prevalence and antigenic specificity of antineutrophil cytoplasmic autoantibodies (ANCA) in patients with systemic sclerosis (SSc). METHODS: Sera from 68 patients with SSc were screened for ANCA by indirect immunofluorescence (IIF) assay and for antibodies to myeloperoxidase (MPO) by ELISA. All sera positive for ANCA on IIF were analyzed for reactivity against antigenic targets other than MPO [bactericidal/permeability-increasing protein (BPI), cathepsin G, lysozyme, elastase, PR3, and lactoferrin]. Twenty-three sera negative for ANCA were also tested for antibodies to BPI and cathepsin G using ELISA. RESULTS: The study included 33 patients with diffuse and 35 with limited SSc. ANCA was detected in 24 of the 68 sera (35.3%). In these 24 sera the antigenic targets were BPI in 14, cathepsin G in 13, and MPO in 8. Sera of 11 patients had reactivity against both BPI and cathepsin G. In sera, that were negative for ANCA, antibodies to BPI (4/23), cathepsin G (3/23), and MPO (1/44) were found in a small proportion of patients. Patients with antibodies to BPI had lower skin score, whereas no patient with antibodies to MPO had renal disease. CONCLUSION: BPI and cathepsin G are the major antigenic targets of ANCA seen in patients with SSc. Patients with antibodies to BPI had lower skin scores.