Clinical Characteristics and Outcomes of Interstitial Lung Disease in Primary Sjögren's Syndrome: A Retrospective Cohort Study.

Objectives: To describe the characteristics of primary Sjögren's syndrome (pSS) patients with interstitial lung disease (ILD) and to assess treatment response. Methods: All patients of pSS from 2010 to 2019 were retrospectively identified. Lung function tests, high resolution computed tomography (HRCT) findings, and treatment outcomes were analysed. Results: Out of 550 patients with pSS, ILD was detected in 33 patients (frequency of 6 %). The mean(±SD) age at the diagnosis of pSS was 50 (± 9.3) years. 28/33(84.8%) were females. ILD onset preceded pSS diagnosis in 2 (6%) patients, simultaneously diagnosed in 21 (63.6%) patients and developed after pSS onset in 10 (30.3%) patients. 5 patients (15.15 %) were asymptomatic for ILD. Non-specific interstitial pneumonia (NSIP) accounted for the most frequent ILD subtype, in 15 patients (45.5%). Mycophenolate mofetil (MMF) was the most frequently used steroid sparing agent, in 25 patients (75.7%). 7 patients were lost to follow up. Response was seen in 22 patients, whereas 3 patients were non responders. There was one mortality due to lower respiratory tract infection-related sepsis. Presence of sicca symptoms [91.5% vs 8.7% (p<0.001)], NSIP pattern of ILD [90% vs 10% (p = 0.002)], and absence of Raynaud's phenomenon [91.7% vs 8.3% (p<0.001)] were significantly associated with responder status when compared to non-responders. Conclusion: ILD in primary Sjögren's syndrome is not an uncommon entity, and immunosuppression with steroids along with steroid-sparing agents led to good clinical outcomes of ILD in a majority of the patients in our cohort.

Transient perivascular inflammation of the carotid artery (TIPIC) syndrome - a rare differential for anterior neck pain - Series of 3 cases and review of literature.

We report a series of 3 cases of transient perivascular inflammation of the carotid artery (TIPIC) syndrome in an otherwise healthy individual. We would also like to review this rare entity and compare it with other similar cases reported in the literature. Our first case was a young male with right-sided neck pain of 1-week duration with magnetic resonance imaging (MRI) showing right carotid perivascular inflammation which completely resolved after 2 weeks with anti-inflammatory drugs. In the second case, a young male presented with left-sided neck pain and odynophagia of 5 days duration with an MRI showing left carotid perivascular inflammation which completely resolved after 2 weeks with anti-inflammatory drugs. In the third case a young male presented with right-sided neck pain of 1-day duration with an MRI showing right common carotid perivascular inflammation near the bifurcation with complete resolution in pain but with residual wall thickening. We want to highlight the existence of this new entity by reporting these 3 case series with a brief review of the literature. The cause and pathogenesis of this rare entity remain unknown. It has been hypothesized to be autoimmune or viral-mediated inflammation which requires further understanding.

Hydroxychloroquine-Induced Phospholipidosis - A Forgotten Complication of a Common Drug.

Hydroxychloroquine (HCQ) has immunomodulatory and immunosuppressive properties and is used in many rheumatological conditions like systemic lupus erythematosus, rheumatoid arthritis, and Sjogren's syndrome. It is usually a widely used and well-tolerated DMARD (Disease Modifying Anti Rheumatic Drugs). Its most feared toxicities include retinopathy and, rarely, cardiomyopathy. Among its other reported side effects is drug-induced phospholipidosis. Here, we report two cases of HCQ-induced phospholipidosis based on renal biopsy electron microscopy. HCQ-induced phospholipidosis, although uncommon, must be considered as one of the differentials in a patient with persistent proteinuria.

Clinical profile of anti-NXP-2 antibody-positive inflammatory myositis and outcome in an Indian population.

INTRODUCTION: Myositis-specific antibodies (MSA) play an important role in the clinical presentation and prognosis of patients with idiopathic inflammatory myositis (IIM). Anti-NXP-2 is one of the newly described MSA. OBJECTIVE: We aimed to describe various clinical presentations associated with anti-NXP2 antibodies and assess response to treatment. METHODS: In this retrospective study, the electronic medical records of all patients who tested positive for anti-NXP2 during June 2019 to April 2022 were screened. Details of demography, clinical presentation, and treatment data were recorded. The anti-NXP2 was tested using the Euro line test kit. Any patient who had an intensity of ≥1+ was considered testing positive. The diagnosis of IIM was reviewed after applying the 2017 European League of Rheumatology (EULAR)/American College of Rheumatology (ACR) criteria of myositis. RESULTS: Among the 660 suspected patients, 470 (71.2%) patients were positive for IIM, and 28 (5.95%) patients were positive for anti-NXP2. From anti-NXP2-antibody positive, 21/470 (4.46%) patients fulfilled criteria for IIM. Among 12 adult (57.14%) patients with IIM, 7 (58.33%) presented as polymyositis (PM) and 5 (41.6%) as dermatomyositis (DM) with median age at presentation of 45 (IQR: 25-58) years. Calcinosis and subcutaneous oedema were observed in 4 (19%) and 2 (9.52%), respectively; myalgia in 6 (28.6%); and distal muscle weakness in 5 (23.8%) patients. Malignancy at the time of diagnosis was observed in two adults with IIM (16.7%), one with DM (intraductal breast cancer), and another with PM (anaplastic large cell lymphoma). Remaining, 9 had juvenile dermatomyositis (JDM) with a median age of 4 (IQR: 3-8) years. Seven (77.8%) patients with JDM had skin rash specific for DM (heliotrope rash and Gottron's papule). None of the patients had cardiac and lung involvement, while GI symptoms, especially dysphagia, were present in 5 (23.8%) patients. During a median follow-up of 19 months (IQR: 12-26 months), 19/19 patients reported improvement and were in remission with treatment. CONCLUSION: The current study shows that adult DM patients with anti-NXP-2 autoantibodies have a unique clinical phenotype. Its presentation differs between adult and JDM, even in different parts of the world. Muscle weakness is mild and responds to treatment. Dysphagia needs more time and aggressive IS for improvement as compared to other muscle involvement. Key Points • Anti-NXP-2 antibody presentation varied from adult to child, as in different parts of the world. • In Indian adult patients, non-specific skin manifestations were more common, whereas in JDM, specific skin features were common. • There was less likely involvement of the lung and heart. But more risk of GI involvement requiring aggressive management. • Adult with anti-NXP-2 antibody should be screened for malignancy at the time of presentation.

Clinical and angiographic outcomes of Mycophenolate versus Methotrexate in South Asian patients of Takayasu arteritis: Results from an open-label, randomised controlled trial.

OBJECTIVE: To compare the clinical and angiographic responses of Mycophenolate Mofetil (MMF) versus Methotrexate (MTX) in Takayasu arteritis (TAK). METHODS: This was a open label, outcome assessor blinded trial. Adult patients of TAK with active disease were randomized 1:1 to MMF 1g twice daily or MTX 20 mg once weekly, by computer generated program. All patients were started on 0.5 mg/kg of steroids with a predetermined tapering protocol. Primary outcome was treatment response as defined by Indian Takayasu arteritis score at 9 months. Secondary end points included time to first failure and angiographic progression. RESULTS: A total of 52 patients (26 in each arm) were recruited. The rate of responders was 71.43% (15/21) in the MMF arm and 63.64% (14/22) in the MTX arm (p=0.58). The median time to 1st failure was 9 months (Range: 3-9) and 4.5 months (range: 3-9) in the MMF and MTX arm respectively (p=0.052). In both groups, 15 % of patients (n=3) had progressive disease in angiography. CONCLUSION: The results showed numerically better outcomes towards MMF, with a longer time to first failure than Methotrexate(9 months versus 4.5 months, p=0.052). No significant difference was seen in the angiographic outcomes.

New-onset Adult-onset Still's disease-like syndrome after ChAdOx1 nCoV-19 vaccination-a case series with review of literature.

We report a series of 3 Adult-onset Still's disease (AOSD)-like presentations in previously healthy females following vaccination with the ChAdOx1 nCoV-19 vaccine, and also compare them with similar cases reported in literature through a PubMed database search. Our first patient had a high spiking bi-quotidian type of fever with myalgia, sore throat, and arthritis with onset 10-day post-vaccination, with laboratory features of hyper inflammation responding to only naproxen. She was off treatment after 2 months. The second patient, with onset 3-week post-vaccination, had a more severe illness, requiring high dose immunosuppression. In our third case, the onset of illness was slightly delayed i.e., 3-month post-vaccination, but she had the most severe disease with macrophage activation syndrome at presentation requiring immunosuppression and biologicals. The underlying mechanism may be linked to the activation of Toll-like receptors (TLR)-TLR-7 and TLR-9-leading to a robust immune response. These 3 cases highlight the immunogenicity of COVID-19 vaccines, with the possibility of occurrence of new-onset systemic hyper-inflammation illness which can happen a few days following the vaccination, sometimes even delayed to months, and can range in severity from mild to even life-threatening. More cases need to be studied to understand the profile and prognosis of these syndromes in the long run.

Unusual Morphological and Automated Hematology Analyzer Features in 3 Cases of B-cell Malignancy-associated Type I Cryoglobulinemic Vasculitis.

Type I cryoglobulins are monoclonal immunoglobulins produced due to underlying hematological malignancy. Cryoglobulins spontaneously precipitate from serum and plasma at low temperatures and become soluble again on rewarming to 37 °C. Processing of blood at temperature lower than 37 °C in the laboratory may cause precipitation of cryoglobulins resulting in interferences in the automated cell counter analysis. We report three patients with cryoglobulinemic vasculitis wherein each case had different morphology of cryoglobulin precipitates on peripheral blood film, like needle shaped bluish-gray crystals, amorphous weakly basophilic extracellular deposits extraneously indenting red blood cells and basophilic neutrophilic inclusions respectively. The effect of cryoglobulins on two technologically different automated cell counters based on principles of impedance, Volume-Conductivity-Scatter (VCS) and fluorescence flow cytometry was assessed. This case series provides interesting insight into the varying morphological features of cryoglobulins on May-Grunwald-Giemsa stained blood films and interference caused by cryoglobulins in different automated cell counter analysis resulting in pseudo-leucocytosis, pseudo-thrombocytosis, abnormal histograms and scatterplots. Identification of these hematologic abnormalities and artifacts induced by cryoglobulins is necessary since it may be the first clue leading to the timely diagnosis of cryoglobulinemia and hence the underlying hematological malignancy, as in our cases.

Update on pregnancy in Takayasu arteritis-A narrative review.

Takayasu arteritis (TA) is a chronic, idiopathic large-vessel vasculitis that affects women of reproductive age, and has significant maternal and fetal implications. Although there are contrasting data on the effect of TA on fertility, most studies have shown that fertility outcomes remain unaffected. The disease activity of TA usually either remains stable or decreases during pregnancy. The important fetomaternal complications are maternal hypertension, pre-eclampsia, prematurity, and intrauterine growth restriction. To reduce maternal and fetal morbidity, controlling the disease before conception is important. This review article discusses the various implications, challenges, and medical and endovascular management of TA during pregnancy.

Mycophenolate in scleroderma-associated interstitial lung disease: Real-world data from rheumatology and pulmonology clinics in South Asia.

Introduction: There is a paucity of real-world data on mycophenolate mofetil/mycophenolate sodium in systemic sclerosis-related interstitial lung disease. Aim: To study the efficacy of mycophenolate mofetil/ mycophenolate sodium in systemic sclerosis-related interstitial lung disease. Methods: In this single-centre study, clinical, laboratory and imaging details of consecutive patients with systemic sclerosis-related interstitial lung disease receiving mycophenolate mofetil/mycophenolate sodium from rheumatology and pulmonology clinics between January 2008 and March 2017 were retrospectively retrieved. The change in percentage of predicted normal forced vital capacity at last follow-up visit as compared with baseline was studied. In addition, high-resolution computed tomography scans at baseline and 2-year follow-up visit were scored as either stable/improved or worsened by experienced thoracic radiologists blinded to the clinical details of patients. Results: Altogether, 88 patients (85.2% females) with mean age (SD) of 33.8 years (± 11.3) and median (interquartile range) duration of disease since non-Raynaud's symptoms of 36 months (13.5-60) were studied. Diffuse systemic sclerosis comprised 85.2% of them. The mean baseline forced vital capacity was 61.2 ± 17.9% and median scores for ground glass opacities and fibrosis in high-resolution computed tomography were 0.5 (0-1.3) and 1 (0-1.3), respectively. At a median follow-up duration of 30 months (interquartile range = 16.5-49), the percentage of forced vital capacity improved by 1.8% (-3.82 to 9.07) as compared with baseline visit (p = 0.02). In the 2-year follow-up, the ground glass opacity and fibrosis scores in high-resolution computed tomography improved in 17.3% and 7.7% of patients and stabilized in 63.5% and 78.8% patients, respectively. Conclusion: Mycophenolate mofetil/mycophenolate sodium was efficacious in improving /stabilizing forced vital capacity irrespective of the baseline high-resolution computed tomography lung scores in our patients with systemic sclerosis-related interstitial lung disease during the ⩾ 2-year follow-up period.

Revisiting cardiac safety of hydroxychloroquine in rheumatological diseases during COVID-19 era: Facts and myths.

Severe acute respiratory syndrome coronavirus 2 has spread across the globe affecting more than 10 million people as of August 2020. With the pandemic spreading at such an alarming rate, a lot of efforts are in the process of identification of an effective treatment at it's earliest. Hydroxychloroquine (HCQ) is such a drug that is being studied as a repurposed agent, although the early results are still inconclusive. However, an important adverse effect that has raised concerns in the recent times is its possible cardiac toxicity, mainly the 'QT,' prolongation in electro-cardiogram, which has created a sense of apprehension for its use in traditional indications like rheumatological conditions. In decades of HCQ use by rheumatologists, this cardiac toxicity was rarely ever seen. So, what is different in the current coronavirus disease 2019 (COVID-19) era? This review outlines various studies on HCQ reporting cardiac adverse events in patients with rheumatic diseases as well as, in patients with COVID-19 infection. In addition, two important observations were noticed; first, the doses that have been used in the current COVID-19 scenario are much higher than what are used in rheumatology. Second, COVID-19 infection may by itself lead to intrinsic cardiac abnormalities, which is probably acting as a confounder. Most of the available and credible data suggest that HCQ is a safe drug, including the RECOVERY trial stating no cardiotoxicity by HCQ. This review reinforces the safety profile of HCQ in a data-driven manner and addresses the concerns of the physicians. However, its cautious use in those with pre-existing cardiac abnormalities cannot be overemphasized.

Comparison of safety, efficacy and cost between oral pulse cyclophosphamide versus intravenous cyclophosphamide pulse therapy in severe systemic lupus erythematosus.

OBJECTIVES: The aim of this study is to compare efficacy, toxicity and cost between oral and intravenous cyclophosphamide (CYC) pulse therapy in inducing remission (Systemic Lupus Erythematosus Disease Activity Index [SLEDAI] <3) in severe SLE. METHODS: We retrospectively checked the hospital records of patients between the years 2000 and 2018, who had been administered oral cyclophosphamide pulse and intravenous (IV) cyclophosphamide pulse. SLEDAI at baseline and after 6 months of therapy were noted. The statistical analysis was done using Mann-Whitney U test. The cost was also calculated. RESULTS: We included 45 patients in this study, 21 in the oral pulse group and 24 in the IV group. The median age of patients in the oral and IV groups were 29 (interquartile range [IQR] 22-37) and 26 (IQR 19.25-0.75) years respectively. Median SLEDAI at baseline was comparable between the 2 groups (oral 18.0 [IQR 15.0-26.0]; IV 14.5 [IQR 11.0-20.0] P = .151). At the end of 6 months of treatment, it was 0.0 (IQR 0.0-4.0) in the oral group, as against 2.0 (IQR 0.0-5.5) in IV group (P = .676). There was no major adverse event in either group. Oral cyclophosphamide pulse therapy was more economical as compared to IV cyclophosphamide [630 Indian National rupees( INR)/ 8.85 US dollars(USD) in the IV arm and 50 INR/0.7 USD in the oral arm] (P < .001). CONCLUSION: This study concludes that oral cyclophosphamide pulse therapy is an economical option and there was no difference in efficacy and safety between oral cyclophosphamide pulse therapy and IV pulse cyclophosphamide therapy.