2015 recommendations for the management of polymyalgia rheumatica: a European League Against Rheumatism/American College of Rheumatology collaborative initiative

Therapy for polymyalgia rheumatica (PMR) varies widely in clinical practice as international recommendations for PMR treatment are not currently available. In this paper, we report the 2015 European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) recommendations for the management of PMR. We used the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) methodology as a framework for the project. Accordingly, the direction and strength of the recommendations are based on the quality of evidence, the balance between desirable and undesirable effects, patients'and clinicians'values and preferences, and resource use. Eight overarching principles and nine specific recommendations were developed covering several aspects of PMR, including basic and follow-up investigations of patients under treatment, risk factor assessment, medical access for patients and specialist referral, treatment strategies such as initial glucocorticoid (GC) doses and subsequent tapering regimens, use of intramuscular GCs and disease modifying anti-rheumatic drugs (DMARDs), as well as the roles of non-steroidal anti-rheumatic drugs and non-pharmacological interventions. These recommendations will inform primary, secondary and tertiary care physicians about an international consensus on the management of PMR. These recommendations should serve to inform clinicians about best practices in the care of patients with PMR

A case of glyburide-induced leukocytoclastic vasculitis

Introduction: Medication-induced leukocytoclastic vasculitis is a small-vessel vasculitis that most commonly manifests with palpable purpuric lesions on gravity dependent areas. Development of the vasculitis occurs within weeks after the initial administration of the medication, with clearance upon withdrawal of the medication. Glyburide, a sulfonylurea medication, is used to treat non-insulin dependent diabetes mellitus. We report a rare case of glyburide-associated leukocytoclastic vasculitis. Observation: We report a 71-year-old man with type 2 diabetes mellitus who presented with palpable purpura on the lower extremities. Cutaneous biopsy revealed superficial small vessel vasculitis with IgA perivascular deposits.  Further questioning revealed three prior episodes of palpable purpura after restarting the glyburide medication, with clearance upon discontinuation. We diagnosed drug-induced vasculitis related to the glyburide. Conclusions: This case highlights a rarely reported cutaneous adverse reaction to the commonly used diabetic medication, glyburide. Physicians should consider cutaneous vasculitis as a potential side effect of glyburide.Abbreviations: LCV (Leukocytoclastic vasculitis), c-ANCA (centrally accentuated anti-neutrophilic cytoplasmic antibody), p-ANCA (Perinuclear anti-neutrophilic cytoplasmic antibody), anti-TNF-alpha (anti-tumor necrosis factor alpha

Protective Role of Mast Cells in Primary Systemic Vasculitis: A Perspective

Mast cells are important cells of the immune system. Although traditionally considered as key players in allergic and hypersensitivity reactions, emerging evidence suggests that mast cells have many complex roles in vascular disease. These include regulation of vasodilation, angiogenesis, activation of matrix metalloproteinases, apoptosis of smooth muscle cells, and activation of the renin angiotensin system. Mast cells are also known to play an immunomodulatory role via modulation of regulatory T-cell (Treg), macrophage and endothelial cell functions. This dual role of the mast cells is evident in myeloperoxidase anti-neutrophil cytoplasmic antibodies-mouse model of glomerulonephritis in which mast cell deficiency worsens glomerulonephritis, whereas inhibition of mast cell degranulation is effective in abrogating the development of glomerulonephritis. Our previous work demonstrated that mast cell degranulation inhibits lipopolysaccharide-induced interleukin 6 (IL-6) production in mice. This effect was not seen in histamine-1-receptor knockout (H1R−/−) mice suggesting a role for histamine in IL-6 homeostasis. In addition, mast cell degranulation-mediated decrease in IL-6 production was associated with an upregulation of suppressor of cytokine signaling-1 protein in the aorta. We propose that mast cells regulate large artery inflammation through T-cells, shifting a primarily Th1 and Th17 toward a Th2 response and leading to enhanced IL-10 production, activation Treg cells, and the inhibition of macrophage functions