Durga Prasanna Misra

A scoping review of the use of non-biologic disease modifying anti-rheumatic drugs in the management of large vessel vasculitis

Takayasus arteritis (TA) and Giant cell arteritis (GCA) comprise the large vessel vasculitides (LVV). Patients with LVV are treated with disease-modifying anti-rheumatic drugs (DMARDs), both conventional (cDMARDs) and biologic (bDMARDs). We undertook a scoping review to assess the effectiveness of cDMARDs in TA and GCA. We could identify 11 studies in TA and 18 studies in GCA. There were only 3 randomized controlled trials on methotrexate, one on hydroxychloroquine and two on cyclosporine in GCA, the others being case series (including all studies on TA). Most of these studies had small patient numbers (median 15 in TA and 27 in GCA). Outcome measures reported in different studies were heterogenous. Overall, methotrexate, leflunomide, azathioprine, mycophenolate mofetil and cyclophosphamide were effective in TA (low quality of evidence). Methotrexate (high quality of evidence), hydroxychloroquine and cyclosporine (moderate quality of evidence) appeared to be ineffective in GCA. Azathioprine (moderate quality of evidence), leflunomide, mycophenolate mofetil, cyclophosphamide and dapsone (low quality of evidence) were effective in GCA. There exists a paucity of high quality evidence to guide use of cDMARDs in TA and GCA. There is an unmet need to conduct large multi-centric randomized placebo-controlled trials to accurately assess the utility on cDMARDs in LVV.

NMR-Based Serum Metabolomics Discriminates Takayasu Arteritis from Healthy Individuals: A Proof-of-Principle Study.

Takayasu arteritis (TA) is a debilitating, systemic disease that involves the aorta and large arteries in a chronic inflammatory process that leads to vessel stenosis. Initially, the disease remains clinically silent (or remains undetected) until the patients present with vascular occlusion. Therefore, new methods for appropriate and timely diagnosis of TA cases are needed to start proper therapy on time and also to monitor the patients response to the given treatment. In this context, NMR-based serum metabolomic profiling has been explored in this proof-of-principle study for the first time to determine characteristic metabolites that could be potentially helpful for diagnosis and prognosis of TA. Serum metabolic profiling of TA patients (n = 29) and healthy controls (n = 30) was performed using 1D (1)H NMR spectroscopy, and possible biomarker metabolites were identified. Using projection to least-squares discriminant analysis, we could distinguish TA patients from healthy controls. Compared to healthy controls, TA patients had (a) increased serum levels of choline metabolites, LDL cholesterol, N-acetyl glycoproteins (NAGs), and glucose and (b) decreased serum levels of lactate, lipids, HDL cholesterol, and glucogenic amino acids. The results of this study are preliminary and need to be confirmed in a prospective study.

Cardiac involvement in primary systemic vasculitis and potential drug therapies to reduce cardiovascular risk

Cardiac involvement is common in primary systemic vasculitides and may be due to direct effect of the disease on the heart or due to therapy. We shall review involvement of the heart in the various forms of primary systemic vasculitis. Among anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV), eosinophilic granulomatosis with polyangiitis most commonly involves the heart. Involvement of the heart confers poorer prognosis in AAV, which is also complicated by increased risk of cardiovascular events. Kawasaki’s disease (KD) is the most common form of medium-vessel vasculitis to affect the heart, with coronary artery aneurysms being the most common manifestation. These predispose patients with KD to develop premature ischemic heart disease. Takayasu’s arteritis is the most common large-vessel vasculitis to involve the heart and can result in aortic incompetence, myocarditis, or coronary heart disease. Involvement of the heart in Behcet’s disease is usually in the form of intracardiac mass lesions, thrombosis, or endomyocardial fibrosis. Drugs used in the treatment of systemic vasculitis influence the risk of developing cardiovascular events. Corticosteroid therapy has been shown to increase the risk of myocardial infarction, whereas methotrexate, azathioprine, mycophenolate mofetil, rituximab, and anti-tumor necrosis alpha agents favorably modulate the risk of cardiovascular events, predominantly by dampening systemic inflammation. Awareness of cardiac involvement in vasculitis and accelerated cardiovascular risk in these patients should help clinicians to maximize the modulation of modifiable risk factors for heart disease in these individuals.

Increased Circulating Th17 Cells, Serum IL-17A, and IL-23 in Takayasu Arteritis

Introduction. Th17, γδT, NK, and NKT cells in peripheral blood and serum IL-17 and IL-23 in Takayasu arteritis (TA) were measured and correlated with disease activity. Methods. Th17 (anti-CD3APC, CD4PECy7, and IL-17PE), NKT, NK (anti-CD3APC, CD56FITC), and γδT (anti-CD3FITC and γδTCRAPC) cells were enumerated by flow cytometry in peripheral blood of 30 patients with TA (ACR1990 criteria) and 20 healthy controls, serum IL-17 and IL-23 measured by ELISA. Relation with disease activity (NIH criteria, ITAS2010) was analyzed (using nonparametric tests, median with interquartile range). Results. Mean age of patients was 33.47 ± 11.78 years (25 females); mean symptom duration was 7.1 ± 5.3 years. 13 were not on immunosuppressants; 12 were active (ITAS2010 ≥ 4). The percentage of Th17 cells was significantly expanded in TA (patients 2.1 (1.5–3.2) versus controls 0.75 (0.32–1.2); p < 0.0001) with no differences in other cell populations. Serum IL-17 and IL-23 (pg/mL) in patients (6.2 (4.6–8.5) and 15 (14.9–26.5), resp.) were significantly higher (p < 0.001) than controls (3.9 (3.9–7.3) and undetectable median value, resp.). Subgroup analysis revealed no correlation of Th17 cells, serum IL-17, and IL-23 with disease activity or medications, nor any significant difference before and after medication. Conclusions. There is significant expansion of Th17 cells and elevated serum IL-17 and IL-23 levels in TA patients compared to healthy controls.

Publishing in black and white: the relevance of listing of scientific journals

Scientific publishing, including in the field of Rheumatology, is evolving rapidly. Predatory journals are one of the major threats to contemporary publishing, especially to eager and naïve authors. In this narrative review, we discuss mechanisms that authors can employ to white list genuine scientific journals and blacklist “predatory” ones. Inclusion of a journal in reputed indices such as Medline (but not just Pubmed), Web of Science, Scopus or Embase raises the likelihood that the journal is genuine, more so if it is included in the current Journal Citation Reports. Other commercially available whitelists also exist, so also whitelists published by regulatory authorities in some countries. A commercially available blacklist has emerged since the very useful Beall’s blacklist became defunct. In the absence of access to a whitelist or blacklist, certain characteristics such as repeated email solicitations for articles with an extremely narrow deadline from unknown sources, lack of inclusion in reputed indices, journals not published or endorsed by national or international society and scarcity of currently published articles should render authors suspicious of the genuine nature of a journal. National societies should work together to generate subject-specific (including Rheumatology specific) whitelists that can be available free of cost to authors from all over the world.

Vasculitis and vasculitis-like manifestations in monogenic autoinflammatory syndromes

Monogenic autoinflammatory syndromes are a rare group of disorders characterized by periodic episodes of systemic inflammation of endogenous origin. Sometimes, these diseases may present with features akin to vasculitis. We conducted a literature review on such vasculitic manifestations in described monogenic autoinflammatory syndromes utilizing the Online Mendelian Inheritance in Man (OMIM), Medline, and Scopus databases. Our search identified that Familial Mediterranean fever (FMF) can manifest with features of either small, medium, large, or variable-vessel vasculitis. Stimulator of interferon gene (STING)-associated vasculopathy of infancy (SAVI) is an interferonopathy that can mimic the presentation of medium-vessel or small-vessel vasculitis, whereas deficiency of adenosine deaminase 2 (DADA2) is another such mimic of medium-vessel vasculitis, associated in a significant number of patients with features of immunodeficiency. Occasional reports exist of vasculitic manifestations in tumor necrosis factor (TNF) receptor-associated periodic fever syndrome (TRAPS) and chronic infantile neurologic cutaneous and articular disorder (CINCA), whereas mevalonate kinase deficiency can also mimic the presentation of small- or medium-vessel vasculitis. Clinicians should be aware of the possibility of autoinflammatory disease presenting as vasculitis to diagnose and treat the same appropriately.

2016 update of the EULAR recommendations for the management of rheumatoid arthritis: a utopia beyond patients in low/middle income countries?

We read with great interest the recently published recommendations by the European League against Rheumatism (EULAR) on the management of rheumatoid arthritis (RA).1 The EULAR recommendations, although primarily targeted towards European countries, are read and followed across the world including low/middle income nations. Consequently, we were disappointed to note that the updated guidelines recommend the use of biological disease-modifying anti-rheumatic drugs (bDMARDs) or targeted synthetic DMARDs (tsDMARDs) immediately following failure of monotherapy with conventional synthetic DMARDs (csDMARDs) in those patients with poor prognostic factors such as seropositivity for rheumatoid factor (RF) or anticitrullinated peptide antibodies (ACPA), highly active disease or early radiographic joint damage (recommendation number 8).1 This is in contrast to the 2015 guidelines provided by the American College of Rheumatology (ACR) for the management of RA,2 which offer the option of either combining csDMARDs or using bDMARDs or tofacitinib (tsDMARD) following failure of methotrexate monotherapy in RA, irrespective of the presence or absence of such poor prognostic indicators. Early use of bDMARDs in the management of RA poses certain specific problems, as discussed below. Rheumatoid arthritis is one of the …

Toxic epidermal necrolysis due to therapy with cyclophosphamide and mesna. A case report of a patient with seronegative rheumatoid arthritis and rheumatoid vasculitis.

Rheumatoid vasculitis usually occurs on the background of seropositive rheumatoid arthritis, although in rare cases the patients can be seronegative. We report a woman with seronegative rheumatoid arthritis with rheumatoid vasculitis who developed toxic epidermal necrolysis involving most of her body surface area, while on therapy with intravenous cyclophosphamide and mesna. After withdrawal of suspected offending agents, administration of intravenous immunoglobulin, and supportive therapy, she had a favorable outcome. Such an occurrence is rare and serves to educate about a potentially life-threatening adverse event associated with a commonly used immunosuppressive agent.ZusammenfassungEine rheumatoide Vaskulitis tritt meist vor dem Hintergrund einer seropositiven rheumatoiden Arthritis auf, selten auch bei Seronegativität. Berichtet wird über eine Patientin mit seronegativer rheumatoider Arthritis, die unter Therapie mit i.v. Cyclophosphamid und Mesna eine toxische epidermale Nekrolyse im Bereich von nahezu der gesamten Körperoberfläche entwickelte. Nach Sistieren der im Verdacht stehenden Substanzen, i.v. Gabe von Immunglobulinen und Implementierung einer supportiven Therapie kam es zu einem günstigen Verlauf und Outcome. Die Schilderung dieses selten vorkommenden Ereignisses soll für eine potenziell lebensbedrohliche Nebenwirkung in Verbindung mit einem häufig eingesetzten Immunsuppressivum sensibilisieren.

Toxic epidermal necrolysis due to therapy with cyclophosphamide and mesna

Rheumatoid vasculitis usually occurs on the background of seropositive rheumatoid arthritis, although in rare cases the patients can be seronegative. We report a woman with seronegative rheumatoid arthritis with rheumatoid vasculitis who developed toxic epidermal necrolysis involving most of her body surface area, while on therapy with intravenous cyclophosphamide and mesna. After withdrawal of suspected offending agents, administration of intravenous immunoglobulin, and supportive therapy, she had a favorable outcome. Such an occurrence is rare and serves to educate about a potentially life-threatening adverse event associated with a commonly used immunosuppressive agent.ZusammenfassungEine rheumatoide Vaskulitis tritt meist vor dem Hintergrund einer seropositiven rheumatoiden Arthritis auf, selten auch bei Seronegativität. Berichtet wird über eine Patientin mit seronegativer rheumatoider Arthritis, die unter Therapie mit i.v. Cyclophosphamid und Mesna eine toxische epidermale Nekrolyse im Bereich von nahezu der gesamten Körperoberfläche entwickelte. Nach Sistieren der im Verdacht stehenden Substanzen, i.v. Gabe von Immunglobulinen und Implementierung einer supportiven Therapie kam es zu einem günstigen Verlauf und Outcome. Die Schilderung dieses selten vorkommenden Ereignisses soll für eine potenziell lebensbedrohliche Nebenwirkung in Verbindung mit einem häufig eingesetzten Immunsuppressivum sensibilisieren.

Splenectomy increases the subsequent risk of systemic lupus erythematosus: a word of caution

This comment refers to the article available at: http://dx.doi.org/10.1007/s00296-015-3388-9 .