Ashish J. Mathew

Infections and arthritis

Bacteria, viruses, fungi, and parasites can all cause arthritis of either acute or chronic nature, which can be divided into infective/septic, reactive, or inflammatory. Considerable advances have occurred in diagnostic techniques in the recent decades resulting in better treatment outcomes in patients with infective arthritis. Detection of emerging arthritogenic viruses has changed the epidemiology of infection-related arthritis. The role of viruses in the pathogenesis of chronic inflammatory arthritides such as rheumatoid arthritis is increasingly being recognized. We discuss the various causative agents of infective arthritis and emphasize on the approach to each type of arthritis, highlighting the diagnostic tests, along with their statistical accuracy. Various investigations including newer methods such as nucleic acid amplification using polymerase chain reaction are discussed along with the pitfalls in interpreting the tests.

Childhood-onset Takayasu arteritis: an update.

Childhood‐onset Takayasu arteritis (c‐TA) is a distinct subset affecting a wide age group, ranging from young infants to adolescents and it differs from adult TA in many aspects. There is scarcity of data on c‐TA worldwide. The disease is classified using the European League Against Rheumatism/Pediatric Rheumatology International Trials Organization/Pediatric Rheumatology European Society criteria. The non‐specific nature of presenting complaints and lack of appropriate biomarkers delay the early diagnosis of this illness and many children present with complications, which become irreversible once they set in. One of the largest cohorts of 40 children with c‐TA from our center reports hypertension as the commonest presenting feature. Systemic symptoms like headache, fever and weight loss are also described. Assessment of disease in c‐TA is done by correlating clinical features with raised inflammatory markers. Advanced imaging plays an important role in diagnosis. In c‐TA, the role of magnetic resonance angiography is advocated, taking into consideration the enormous amount of radiation exposure with other modalities. Complications of c‐TA include cardiovascular, pulmonary, neurological and those arising secondary to long‐term steroid and immunosuppression therapy.

MRI and ultrasound in rheumatoid arthritis.

Purpose of reviewTo overview the recent literature on the use of MRI and musculoskeletal ultrasonography (MSUS) in rheumatoid arthritis. Recent findingsSubclinical inflammation has been widely confirmed, even in the earliest phases of rheumatoid arthritis. The presence of osteitis has added benefits to modern diagnostic criteria, and anticitrullinated peptide antibody positive patients have demonstrated higher osteitis scores. A model for prediction of rheumatoid arthritis onset employing usual clinical data and power Doppler ultrasonography has been reported. The presence of tenosynovitis may also be an early finding in rheumatoid arthritis. Modern imaging continues to inform our concept of pathogenesis with reports on the direct relationship of synovitis to cartilage proteoglycan loss using compositional MRI measures. Growing data on the validity of MRI as an important predictor of clinical and radiographic damage endpoints has been reported and reflected in the growing use of this outcome in many contemporary biologic therapy trials. Much work has been presented on improved and validated MSUS scores with reduced and feasible joint counts. The role of ultrasonography in making sensible decisions when monitoring biologic use, and in tapering, has been reported. SummaryThe recent literature demonstrates improved validity and utility for both MRI and MSUS in diagnosis, prognosis and monitoring of rheumatoid arthritis.

Wegener's granulomatosis : a rare presentation

Wegener’s granulomatosis (WG) is a necrotizing granulomatous vasculitis involving the nose, paranasal sinuses, lungs, and kidneys. There are two types of WG—systemic, which is characterized by focal segmental necrotizing glomerulonephritis and limited in which the kidneys are spared. Without proper immunosuppression, WG can be aggressive and often fatal. There are very few reports on WG presenting as parotitis and lacrimal gland involvement. We report a lady who presented recurrent parotitis, focal segmental glomerulosclerosis, and orbital cellulitis, in whom the final diagnosis was revealed after an open lung biopsy.

Psoriatic arthritis: lessons from imaging studies and implications for therapy

ABSTRACT Introduction: Modern imaging may aid in the diagnosis, prognosis and monitoring of therapeutic response in psoriatic arthritis (PsA). Detection of osteitis and technical advances like whole body magnetic resonance imaging (MRI) exemplify the value of this technology. Areas covered: Ultrasound (US) provides a clinic-based tool for evaluating both joint pathologies and extra-articular structures (especially enthesitis) including skin and nail disease. Recent studies have demonstrated subclinical disease in psoriasis without arthritis, as well as in PsA, with implications for diagnosis and treatment classification. Modern imaging can also facilitate decisions on tapering of expensive biologics, though real-world clinical studies are still lacking. Expert commentary: The increase in novel PsA therapies should increase the utilization of modern imaging, providing both increased validation of imaging biomarkers as well as responsive outcome measures.

AB1041 Office Extremity Magnetic Resonance Imaging (E-MRI) Can Differentiate Psoriatic and Rheumatoid Arthritis Without Contrast Enhancement

Background Psoriatic arthritis (PsA), especially with symmetric polyarticular presentation, can often mimic rheumatoid arthritis (RA) clinically. Diagnosis of PsA can be challenging in patients without typical skin or nail lesions and in seronegative RA. Office e-MRI of small joints of hands could have a differential diagnosis value in addressing this issue. Objectives The aim of this observational cohort study was to compare typical MRI findings of the hand in patients with PsA and RA. A secondary objective was to evaluate the reliability of two independent readers in scoring the OMERACT-RAMRIS and PsAMRIS-H variables, using a low field magnet office e-MRI machine, without contrast enhancement. Methods Patients classified as PsA (CASPAR) and RA (2010 ACR/EULAR criteria), with symptomatic involvement of hand joints, attending a single tertiary care Rheumatology clinic between July 2013 and October 2014 were included and matched for age and disease duration. Demography, clinical and serological details were retrieved from electronic medical records. All patients underwent MRI of the dominant hand using standard protocols (3DT1-Cor, GESTIR-Cor, TSE-Tra, STIR-Tra, SE-Sag) in a 0.2T Esaote C-scan; Genova, Italy. Images were evaluated independently by two blinded readers in accordance with the OMERACT-RAMRIS and PsAMRIS-H scoring recommendations. Inter-observer reliability was calculated using correlation coefficient method. Univariate analysis of RAMRIS and PsARMRIS-H variables was done using parametric tests. Results Eighteen patients were imaged in each group. Inter-rater reliability was excellent (ICC >0.9) for erosions and synovitis and very good (ICC >0.7) for tenosynovitis and bone marrow edema (BME). Diaphyseal bone marrow edema (DME), periosteal inflammation (PI) and flexor tenosynovitis (FT) at the first interphalangeal joint were exclusively present in PsA patients. Table 1 depicts the salient findings: Conclusions Office e-MRI can distinguish PsA and RA without contrast enhancement, with PI, DME and FT as significant determinants. Excellent inter-rater reliability was noted in this study. This advanced imaging is patient friendly, economical as compared to the conventional MRIs, easily reproducible and can be used in outpatient clinics to aid in the differential diagnostic process in patients in whom diagnosis cannot be established unequivocally. References Mathew AJ, Crues JV, Danda D. Office e-MRI: viewing joints from the inside. Int J Rheum Dis 2014;17:706-9. Ostergaard M, Edmonds J, McQueen F, et al. An introduction to the EULAR-OMERACT rheumatoid arthritis MRI reference image atlas. Ann Rheum Dis 2005;64(Suppl 1):3-7. Ostergaard M, McQueen F, Wiell Charlotte, et al. The OMERACT PsAMRIS: Definitions of key pathologies, suggested MRI sequences and preliminary scoring system for PsA hands. J Rheumatol 2009;36:1816-24 Disclosure of Interest None declared

Office e‐MRI: viewing joints from the inside

Till recently, rheumatology lacked the kudos of hightech interventions and investigation to attract young physicians into the specialty. This is despite the availability of newer biomarkers, emphasis on early or preclinical disease, ‘treat to target’ approach and addition of a wide range of biologics in the therapeutic armamentarium. The introduction of office extremity-MRI (e-MRI) has been a turning point in rheumatology practice that has largely been unnoticed. Since their discovery X-rays have been part of rheumatology practice, and the newer imaging modalities have now become an extension of the clinical examination. Failure of plain radiographs to detect early changes, radiation hazards of computed tomography and strong operator dependence in ultrasonography led to increasing popularity of magnetic resonance imaging (MRI) in rheumatology from its introduction in the early 1980s. Lack of radiation, 3D imaging, higher resolution and better soft tissue contrast are a few of its strengths. However, the biggest gain of MRI over other imaging modalities is its ability to visualize bone marrow edema (osteitis), a marker of inflammation in the pre-erosion stage. Synovium, cartilage and tendons can also be studied in detail through this technique. MRI is also being increasingly used in clinical trials as a marker of outcome. The concept of office e-MRI, in which only the extremity of interest is positioned in the magnet bore, is fairly recent and is gaining popularity. Hassle-free, lowcost installation in the clinics, easy maintenance, lack of magnetic shielding and patient convenience are some of its advantages over high-field systems. Generally these machines have a low-field magnet. The Applause 0.2-T MV-R by MagneVu (Carlsbad, CA, USA) was one of the first e-MRIs, with limited field of view. Currently available e-MRI systems with better sensitivity include the 0.2-T C-scan (Fig. 1) and E-scan, 0.25-T S-scan and 0.31-T O-scan (Esaote SpA, Genoa, Italy). These machines differ in terms of field of view, number of joints that can be imaged and strength of magnets. Optima MR430s 1.5-T (GE Healthcare, Little Chalfont, UK) is the latest addition to the ever-growing series of extremity MRIs, with a powerful 1.5-T magnet, which can be installed in a small area. The main disadvantage of e-MRI systems is that their signal-to-noise ratio is markedly lower than high-field systems and they offer a more limited field of view. Some of these deficiencies can be overcome to a degree by increasing voxel volume or acquisition time using 3D Fourier transformation imaging and optimized pulse sequences. Diagnostic performance of low-field magnets (< 1-T), as compared to conventional high-filed (> 1-T) counterparts has been a long-debated topic, ever since e-MRIs were introduced. Correlation between the performance of extremity and conventional whole-body scanners has been well studied. Taouli et al. have noted that a high-field magnet is not needed to detect early rheumatoid arthritis (RA). A study by Olech et al. comparing 40 patients with healthy controls using a low-field magnet has shown that osteitis is 82.5% specific and 65% sensitive for the diagnosis of RA (Fig. 2). Single erosion was 90% sensitive, but only 35% specific and eliminating lunate from bone edema scoring increased the specificity to 87.5%, marginally reducing the sensitivity. Ejbjerg et al. concluded that 0.2-T MRI provided high accuracy for detection of erosions and synovitis when compared with 1-T high-field imaging, but its sensitivity for detecting bone edema was only 39%. This may be interpreted as a potential deficiency of e-MRI systems, as osteitis is considered to be a predictor of erosions. However, technology for low-field scanners has markedly improved in the years following Correspondence: Dr. Ashish Jacob Mathew Deptartment of Clinical Immunology & Rheumatology, Christian Medical College, Vellore, India Email: ashishjacobmathew@gmail.com

Podocyte Infolding Glomerulopathy (PIG) in a Patient With Undifferentiated Connective Tissue Disease: A Case Report

Podocyte infolding glomerulopathy (PIG) is a recently described pathologic entity characterized by diffuse podocyte infolding into the glomerular basement membrane (GBM) associated with ultrastructurally demonstrable microspherular aggregates. The clinical features, significance, and pathogenesis of this condition are still not well delineated because only a few cases have been documented to date, all from Japan. We report a case of PIG associated with undifferentiated connective tissue disease in an Indian woman who presented with nephrotic syndrome while undergoing treatment for an autoimmune disorder. Ultrastructural analysis of the kidney biopsy specimen revealed unusual subepithelial aggregates of microspherules admixed with few microtubules alongside extensive infolding of podocyte foot processes into the underlying GBMs. Characteristic clustering of these microparticles near the invaginated tips of podocyte foot processes in the GBM was observed on transmission electron microscopy. The patients clinical condition responded favorably to immunosuppressive therapy. The clinical, light microscopic, and diagnostic electron microscopic features of this condition are highlighted in this report in an attempt to contribute some insights into the possible pathogenetic mechanisms of this obscure entity.

Utility of Plain Radiographs in Metabolic Bone Disease – A Case-Based Pictorial Review from a Tertiary Centre

Summary In this era of advanced high-tech imaging, the utility of plain radiographs in conditions of the bone is increasingly being overseen by both clinicians and radiologists. Plain radiography is the first-line, essential screening or diagnostic tool for diverse bone diseases, where magnetic resonance imaging (MRI) may be non-contributory. Plain radiographs often play a pivotal role in diagnosing metabolic bone disorders. This paper from a single tertiary care centre discusses ten real-life patients with metabolic bone conditions and other bone diseases with near-normal MRI of the spine, in whom plain radiographs revealed subtle findings and aided in making diagnoses. Each of these cases had a non-specific clinical presentation. They all showed inconclusive features on MRI, but subtle important radiographic findings led to a specific diagnosis. Plain radiography is key in diagnosing bone diseases. Many of these metabolic conditions clinically mimic rheumatologic conditions owing to non-specific arthralgia and back pain. Familiarity with subtle radiographic findings of these conditions may lead to early diagnosis and treatment, resulting in improved patient outcomes.

THU0322 Descriptive study of asian indian patients with rheumatoid vasculitis in retrospect: a single, tertiary care centre experience

Background Rheumatoid vasculitis (RV) is a severe extra-articular manifestation of rheumatoid arthritis (RA), with high morbidity and mortality reported in literature Objectives To describe the Asian Indian perspective on RV patients, their clinico-laboratory features and their outcome along with the factors affecting them Methods A retrospective review of electronic medical records of 8984 RA patients from January 2007 to August 2016, was done for those satisfying Scott & Bacon criteria for RV1. Probable RV was defined as patients not satisfying Scott & Bacon Criteria, but were managed like RV after exclusion of alternate diagnosis. Birmingham Vasculitis activity score (BVAS) version 32 was used for monitoring activity of RV Results 63 patients of RV were identified, with a study period prevalence of 0.7%, in our RA cohort. 33 (52.4%) patients were female. Mean age of patients was 50.7±11.5 years with median duration of RA being 6 years. Involvement of Peripheral Nervous System (PNS) was the commonest manifestation of RV in 52/63 (82.5%) patients followed by skin in 34/63 (53.9%) patients. Rheumatoid Nodule was seen in 14/ 63 (22.2%) patients. Percentage of current and ex-smokers combined,was same as rheumatoid nodule prevalence. 52 (82.5%) patients had biopsy evidence of vasculitis.26/51 (50.9%)patients were started on mycophenolate mofetil, 13/51 (25.5%)patients on cyclophosphamide, 8/51 (15.7%) patients on azathioprine, 4/51 (7.8%) patients on Methotrexate as immunosuppressive (IS) agent along with mean dose of 46.6±13.7 (0.86±0.23mg/kg/day) prednisolone. Additionally, Rituximab & IVIg were used in 2 patients each respectively. 3 months after initiation of immunosuppression 26/50 (52%) patients on follow-up were in remission and 39/47 (82.9%) patients attained remission at 6 months. Mean time to achieve remission was 151.1±86.3 days. All IS agents were equally effective in inducing remission at 3 and 6 months and showed statistically similar BVAS reduction at 3 and 6 months from baseline (t test & chi-square test). 7 (11.2%) deaths noted in the cohort at their respective last visit during 195.3 patient years cumulative follow up. Multiple regression analysis showed that at baseline, presence of PNS involvement, eosinophilia, thrombocytosis, higher BVAS score and higher steroid requirement were predictors of persistently active vasculitis and absence of eye involvement and higher hemoglobin % at baseline were predictors for remission, at 3 months (p<0.05). 4/50 (8%) patients had relapse of vasculitic symptoms. 2 and 5 year survival rates were 96.2% and 83.9% respectively Conclusions Our cohort of Asian Indian RV was comparitively younger with lesser RA duration, less percentage of ever-smokers, lesser rheumatoid nodule prevalence, higher PNS involvement with better survival/mortality rates compared to published literature. All IS agents showed equal rates of BVAS remission & BVAS reduction at 3 and 6 months of treatment References Scott DG, Bacon PA. Intravenous cyclophosphamide plus methylprednisolone in treatment of systemic rheumatoid vasculitis. Am J Med. 1984 Mar;76(3):377–84. Mukhtyar C, Lee R, Brown D, Carruthers D, Dasgupta B, Dubey S, et al. Modification and validation of the Birmingham Vasculitis Activity Score (version 3). Ann Rheum Dis. 2009 Dec;68(12):1827–32. Disclosure of Interest None declared