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Concept: Cyclophosphamide


Accompanying the increased use of biologic and non-biologic antirheumatic agents, patients with RA have been exposed to an increased risk of Pneumocystis jirovecii infection, which causes acute fulminant P. jirovecii pneumonia (PCP). Mortality in this population is higher than in HIV-infected individuals. Several guidelines and recommendations for HIV-infected individuals are available; however, such guidelines for RA patients remain less clear. Between 2006 and 2008 we encountered a clustering event of P. jirovecii infection among RA outpatients. Through our experience with this outbreak and a review of the recent medical literature regarding asymptomatic colonization and its clinical significance, transmission modes of infection and prophylaxis of PCP, we have learned the following lessons: PCP outbreaks among RA patients can occur through person-to-person transmission in outpatient facilities; asymptomatic carriers serve as reservoirs and sources of infection; and short-term prophylaxis for eradication of P. jirovecii is effective in controlling PCP outbreaks among RA outpatients.

Concepts: Epidemiology, Rheumatoid arthritis, Rheumatology, Methotrexate, Cyclophosphamide, Disease-modifying antirheumatic drug, Hydroxychloroquine, Sulfasalazine


Lupus nephritis is a common and severe manifestation of systemic lupus erythematosus, and an important cause of both acute kidney injury and end-stage renal disease. Despite its aggressive course, lupus nephritis is amenable to treatment in the majority of patients. The paradigm of immunosuppressive treatment for lupus nephritis has evolved over the past few decades from corticosteroids alone to corticosteroids combined with cyclophosphamide. Sequential treatment regimens using various agents have been formulated for induction and long-term maintenance therapy, and mycophenolate mofetil has emerged as a standard of care option for both induction and maintenance immunosuppressive treatment. The current era has witnessed the emergence of multiple novel therapeutic options, such as calcineurin inhibitors and biologic agents that target key pathogenetic mechanisms of lupus nephritis. Clinical outcomes have improved in parallel with these therapeutic advances. This Review discusses the evidence in support of current standard of care immunosuppressive treatments and emerging therapies, and describes their roles and relative merits in the management of patients with lupus nephritis.

Concepts: Nephrology, Corticosteroid, Systemic lupus erythematosus, Glomerulonephritis, Immunosuppressive drug, Lupus nephritis, Cyclophosphamide, Mycophenolic acid


Mycophenolate mofetil (MMF) is used for prevention of allograft rejection in transplantation medicine. In dermatology it is used as a corticosteroid-sparing agent. The pharmacokinetics of MMF are known to vary by individual. Therapeutic dose monitoring of mycophenolic acid (MPA), the active metabolite of MMF, is used as a guide in transplantation medicine, but limited data exist on the benefit of measuring MPA levels in the management of dermatologic disease.

Concepts: Pharmacology, Medicine, Disease, Organ transplant, Cyclophosphamide, Mycophenolic acid, Mycophenolate mofetil, Dermatology


Systemic lupus erythematosus (SLE) is a prototype autoimmune disease characterized by systemic inflammation and autoantibody production. Anti-MBL autoantibodies have been studied in SLE for their possible effect on MBL levels and functional activity. This study aimed at detection of anti-MBL autoantibodies in Indian SLE patients and evaluates their relationship with related immunological parameters. Two hundred diagnosed SLE patients from Western India were included in the study where 87 patients were lupus nephritis (LN) (43.5 %) and remaining (56.5 %) were non-LN. Disease activity was assessed using the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). Anti-MBL autoantibodies to IgG and IgM isotypes, anti-C1q autoantibodies, MBL levels and circulating immune complex levels were detected by ELISA. C3, C4 and CRP levels were detected by nephelometer. Anti-MBL autoantibodies were detected in 52 % SLE patients, where 55 % had IgG-anti-MBL, 33.8 % had IgM-anti-MBL and 11.3 % had both subclasses. Low MBL levels were present in 64.4 % anti-MBL positives as compared with 61.5 % in anti-MBL negatives. Among anti-MBL positives, 74 % had anti-C1q antibodies, whereas 41.7 % of anti-MBL negatives had anti-C1q autoantibodies (p = 3.45E06). An inverse correlation was observed between serum MBL and CIC levels. A statistically significant difference was noted between anti-MBL positives and anti-MBL negative patients with hsCRP levels (p = 0.002). Occurrence of infections was higher among anti-MBL positives (65 %) as compared with anti-MBL negatives (35 %). The difference between SLEDAI scores among anti-MBL positive and negative groups was statistically insignificant. Anti-MBL autoantibodies in SLE patients can influence functional activity of MBL and have a significant role in SLE disease pathogenesis.

Concepts: Immune system, Rheumatoid arthritis, Rheumatology, Systemic lupus erythematosus, Lupus erythematosus, Glomerulonephritis, Lupus nephritis, Cyclophosphamide


This study compares the expression levels of tumor necrosis factor ligand superfamily member 4 (TNFSF4) and TNF-R-associated factor 2 (TRAF2) mRNAs in peripheral blood mononuclear cells (PBMCs) of patients with systemic lupus erythematosus (SLE) against healthy controls. The association of SLE disease activity index (SLEDAI) and clinical features of SLE with altered expression levels of TNFSF4 and TRAF2 mRNAs were also evaluated.

Concepts: Cell nucleus, Rheumatology, Systemic lupus erythematosus, Lupus erythematosus, Glomerulonephritis, Lupus nephritis, Cyclophosphamide, Antiphospholipid syndrome


Leukostasis is a poorly understood and life-threatening complication of acute hyperleukocytic leukemia. The incidence of hyperleukocytosis and leukostasis differs among various subtypes of leukemias. While the pathophysiology of leukostasis is not fully understood, recent research has elucidated many novel pathways that may have therapeutic implications in the future. Respiratory and neurological compromise represents the classical clinical manifestations of leukostasis. If it is not diagnosed and treated rapidly, the one-week mortality rate is approximately 40%. Targeted induction chemotherapy is an important component of the successful treatment of leukostasis, although other modalities of cytoreduction are being used and investigated. Copyright © 2016 John Wiley & Sons, Ltd.

Concepts: Epidemiology, Cancer, Blood, Medical statistics, Bone marrow, Chemotherapy, Leukemia, Cyclophosphamide


Intravenous (IV) cyclophosphamide has been first-line treatment for inducing disease remission in lupus nephritis. The comparative efficacy and toxicity of newer agents such as mycophenolate mofetil (MMF) and calcineurin inhibitors are uncertain.

Concepts: Systemic lupus erythematosus, Immunosuppressive drug, Lupus nephritis, Cyclophosphamide, Mycophenolic acid, Mycophenolate mofetil, Calcineurin


Medications for rheumatoid arthritis (RA) may affect survival. However, studies often include limited follow-up and do not account for selection bias in treatment allocation. Using a large longitudinal database, we examined the association between prednisone use and mortality in RA, and whether this risk was modified with concomitant disease-modifying antirheumatic drug (DMARD) use, after controlling for propensity for treatment with prednisone and individual DMARDs.

Concepts: Immunology, Rheumatoid arthritis, Methotrexate, Cyclophosphamide, Disease-modifying antirheumatic drug, Hydroxychloroquine, Sulfasalazine, Sodium aurothiomalate


This collaboration between the American College of Rheumatology and the American Association of Hip and Knee Surgeons developed an evidence-based guideline for the perioperative management of antirheumatic drug therapy for adults with rheumatoid arthritis (RA), spondyloarthritis (SpA) including ankylosing spondylitis and psoriatic arthritis, juvenile idiopathic arthritis (JIA), or systemic lupus erythematosus (SLE) undergoing elective total hip (THA) or total knee arthroplasty (TKA).

Concepts: Osteoporosis, Rheumatoid arthritis, Rheumatology, Corticosteroid, Systemic lupus erythematosus, Autoimmune diseases, Arthritis, Cyclophosphamide


Depression is a major public health problem among adults with arthritis and other rheumatic disease. The purpose of this study was to conduct a systematic review of previous meta-analyses addressing the effects of exercise (aerobic, strength or both) on depressive symptoms in adults with osteoarthritis, rheumatoid arthritis, fibromyalgia and systemic lupus erythematous.

Concepts: Osteoporosis, Rheumatoid arthritis, Rheumatology, Corticosteroid, Systemic lupus erythematosus, Lupus erythematosus, Arthritis, Cyclophosphamide