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© Dirk Biddle
Granulomatous vasculitis is a subset of systemic necrotizing vasculitis. Granulomas form in response to inflammatory stimuli such as mycobacteria, fungi, and inert materials such as silica and beryllium. A granuloma is an abnormal structure built from at least two activated macrophages adhering to one another which serve to wall off foreign particles. Pathogenesis in the case of the vasculitides remains largely unknown, although recent advances suggest an important role for certain pro-inflammatory cytokines such as tumor necrosis factor-alpha (1). The presence of granulomas is dependent on the type of leucocytic infiltrate and may involve the blood vessel, an adjacent tissue, or a distant site. Granulomas are chronic inflammatory lesions characterised by aggregates of mononuclear inflammatory cells, such as macrophages, surrounded by a rim of lymphocytes and often containing multinucleated giant cells. Sometimes eosinophils and plasma cells are present also. The pattern of inflammation is initiated and maintained by sensitized CD4+ helper T-cells (TH1) via the production of cytokines. Some granulomas may vanish as soon as the disease is effectively treated (2), others may over time become encapsulated by a fibrotic rim and sometimes the centre becomes necrotic.
The presence of granuloma may be used to distinguish some vasculitides. Granulomatous vasculitis conditions include CNS vasculitis, Churg-Strauss syndrome (Eosinophilic granulomatous vasculitis), Giant cell arteritis, Takayasu’s arteritis and of course, Wegener’s granulomatosis. Crohn’s disease has also been associated with a secondary granulomatous vasculitis.
Kawasaki disease is neither a necrotising nor a granulomatous vasculitis, however, the terms granulomatous and necrotising can be used as useful descriptors in conjunction with other factors (such as vessel size) to characterise and distinguish vasculitis conditions.
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1. Marquez, J., Flores, D., Candia, L. & Espinoza, L. (2003) Granulomatous vasculitis. Current Rheumatology Reports, 5, 128-135
2. http://www.pathguy.com/lectures/inflamma.htm
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Mycobacteria: Bacteria with unusual cell walls that are resistant to digestion, being waxy, very hydrophobic and rich in lipid, especially esterified mycolic acids. Staining properties differ from those of gram-negative and gram-positive organisms, being acid-fast. Many are intracellular parasites, causing serious diseases such as leprosy and tuberculosis. Mycobacteria cell walls have strong immunostimulating (adjuvant) properties due to muramyl dipeptide (MDP). Mycobacterium bovis causes tuberculosis in cattle, attenuated strain is Bacille Calmette-Guerin (BCG), used for immunisation. Mycobacterium leprae is the causative agent of leprosy. Mycobacterium microti is a mycobacterium that causes tuberculosis like disease in small rodents (Microtus microtus is the vole), will infect mice but not humans and is therefore much used as a laboratory model. Releases large amounts of cAMP which may inhibit lysosome phagosome fusion. Mycobacterium tuberculosis Is an obligate anaerobic nonmotile bacterium, causative agent of tuberculosis in humans. Lives intracellularly in macrophages. (OMD)
Pathogenesis: The origin and development of disease
Cytokine: Substance produced by a leucocyte that acts upon another cell. Small proteins or biological factors (in the range of 5-20 kD) that are released by cells and have specific effects on cell-cell interaction, communication and behaviour of other cells. Not really different from hormones, but the term tends to be used as a convenient generic shorthand for interleukins, lymphokines and several related signaling molecules such as TNF (tumour necrosis factor alpha) and interferons. Generally growth factors would not be classified as cytokines, though TGF is an exception. Rather an imprecise term. Chemokines are a subset of cytokines. (OMD)
Tumor Necrosis Factor-Alpha: Tumor necrosis factor alpha (TNF-±) is a multifunctional proinflammatory cytokine with effects on lipid metabolism, coagulation, insulin resistance, and endothelial function. It is produced primarily by activated macrophages. It is found in synovial cells and macrophages in the tissues.
It shares many properties with another cytokine - interleukin 1. It occurs in many inflammatory diseases and also as a response to endotoxins from bacteria (for example).
Granuloma: Chronic inflammatory lesion characterised by large numbers of cells of various types (macrophages, lymphocytes, fibroblasts, giant cells), some degrading and some repairing the tissues. (OMD)
Leucocyte: (White Blood Cell) A cell which circulates in the blood and lymphatic system and harbours in the lymph glands and spleen. They are part of the immune system responsible for both directly (T-cells and macrophages) and indirectly (B-cells producing antibodies) attacking foreign invaders of the body. They are colourless, lack haemoglobin, contain a nucleus, and include the lymphocytes, monocytes, neutrophils, eosinophils, and basophils. (OMD)
Chronic: 1a: marked by long duration, by frequent recurrence over a long time and often by slowly progressing seriousness
b: suffering from a disease or ailment of long duration or frequent recurrence
2a: having a slow progressive course of indefinite duration- used especially of degenerative invasive diseases, some infections, psychoses and inflammations
b: infected with a disease-causing agent (such as a virus) and remaining infectious over a long period of time but not necessarily expressing symptoms (eg; chronic carriers may remain healthy but still transmit the virus causing hepatitis B). (M+)
Lesions: Explanation coming soon
Mononuclear: Having only one nucleus
Giant Cells: A cell of large size, often with many nuclei. They are multinucleated masses produced by the fusion of many cells.
They are often associated with viral infections. In AIDS, they are induced when the envelope glycoprotein of HIV binds to the CD4 antigen of uninfected neighboring T4 cells.
The resulting syncytium leads to cell death and thus may account for the cytopathic effect of the virus.
Plasma: The fluid part especially of blood, lymph, or milk that is distinguished from suspended material. (M+)
Fibrotic: Affected or characterised by fibrosis
Necrosis: The sum of the morphological changes indicative of cell death and caused by the progressive degradative action of enzymes; it may affect groups of cells or part of a structure or an organ. (OMD)