Vasculitis literally means inflammation of a vessel or vessels. For the majority of situations it is arteries or arterioles that are affected. This reduces blood flow and produces ischemic necrosis. Ischemia results in anything from immediate infarction at one end of the spectrum to atrophy of the skin at the other (aka atrophic dermatopathy).
The lesion of vasculitis in a vessel varies from fibrinoid necrosis to fibrosis of the wall at the other. The number and type of cell with the lesion of vasculitis varies too. Lesions can be generalised or localised within a vessel.
The lesions that result from vasculitis vary considerably too. Each species have common clinical situations that helps reduce the potential causes and diseases. I will deal with these in each site dedicated to each species.
The most dramatic outcome of vasculitis is an infarct or infarcts. The dead skin will either slough and ulcerate, or will mummify. At the other end of the spectrum is thinning of the skin and alopecia.
In this section, I will go into details about vasculitis in general including the vasculitis pattern, normal anatomy and histology, and then the nomenclature of vasculitis.
Histological changes in vasculitis involve the vessels and the portion of skin and subcutis supplied by the vessel. If you look at the vessels and see vasculitis, the rest is easy. The well prepared examine the vessels first. Once you see vasculitis, it is easy to see the secondary effects. Sometimes or oftentimes, the lesion in the vessel is not visible in the section. You can work in reverse by identifying the unique changes and make a diagnosis without seeing the classic vascular changes.
Cutaneous infarcts are usually wedge-shaped. The necrotic epidermis is wider than the dermal lesion which is wider than the subcutaneous lesion. There is a distinct difference between affected and the adjacent normal tissues.
Ischemic dermatopathy is the other extreme. The changes are typically a thin epidermis with a cell poor cytotoxic/interface pattern and follicular atrophy.
Backel KA, Bradley CW, Cain CL, Morris DO, Goldschmidt KH, Mauldin EA. Canine Ischaemic Dermatopathy: A Retrospective Study of 177 Cases (2005-2016).Vet Dermatol 2019 ;30: 403-e122.
Blood vessels of the body are the arteries, arterioles, capillaries, venules and veins.
Arteries have a narrow lumen compared to their wall thickness and their thickest layer is the muscle layer.
Large, elastic, conducting arteries
On the arterial side, there are the large arteries - also called elastic arteries. They have much elastin and collagen in the tunica media. These are the aorta, carotid, subclavian, axillary, brachial, renal, iliac, and femoral arteries. They are also called conducting or conduit arteries.
There are no large vessels in the organs, so skin does not get large vessel vasculitis.
Medium sized, muscular, distributing arteries
Arteries with mostly smooth muscle in their tunica media that distribute blood to organs are called medium sized arteries. They are muscular arteries and they are also called distributing arteries. They have an internal elastic lamina.
Cutaneous arteries are distributing arteries, and thus medium sized arteries.
Arterioles (resistance vessels)
Arterioles join muscular arteries to the capillaries. They are called resistance vessels and they have smooth muscle that is 1 to 2 smooth muscle cells thick. They have no internal elastic lamina. Arterioles impede blood flow and are responsible for the resistance of blood flow and therefore distribution of blood through an organ. They can be involved in rapidly increasing blood pressure to maintain normal blood pressure.
Vascular smooth muscle cells surround arterioles. These form a continum with pericytes.
Capillaries are where fluids leave the vasculature and return. This fluid movement refreshes the intercellular fluid of the body. Capillaries are one endothelial cell thick. This makes them a semipermiable membrane with a capacity to actively alter their permeability. Capillaries are less than 10um diameter and most are 5um.
Pericytes form a mesh that surrounds capillaries and venules. They are specialised cells that provide support for and constrict capillaries. Relaxation of pericytes is important in controlling blood flow in organs. Pericytes are a diverse population. They are responsible for the blood brain barrier and the blood eye barrier - both situations where there are large numbers of pericytes - one per endothelial cell. They have stem cell qualities and are involved in angiogenesis.
Arteriole smooth muscle transitions to a hybrid smooth muscle cell - pericyte. Mesh pericytes surround the arteriolar endothelial cells. These give way to thin strand or helical pericytes around capillaries. Mesh pericytes are also around endothelial cells of the post capillary venule.
Pericytes or perivascular stem cells express CD34 (Stem cell marker), PDGFRB and CD146. Those in arterioles also express alpha smooth muscle actin (SMA) and Neural Glial antigen 2 (NG2).
Veins carry blood from capillaries to the heart or to a second capillary bed in the case of portal veins. Veins have a wide lumen compared to their wall thickness. The come in small, medium and large sizes, or venules, collecting veins and great veins. The adventitia of veins is the thickest layer.
Venules (small veins)
These are the smallest veins, and include the post capillary venules, which have no muscular layer. Venules have a tunica adventitia and an endothelial layer, and an incomplete muscle layer. Medium and large veins have a complete muscle layer and the adventitia becomes thicker with size.
Blood vessels are divided histologically into 3 layers. In Latin these are Tunica interna, Tunica media and Tunica externa, and in English intima, media and adventitia.
The intima includes the endothelial cells, the subendothelial layer and the internal elastic lamina of arteries, and the elastic network of arterioles. Veins do not have an elastic network of internal elastic lamina.
The media includes the smooth muscle cells, and in the arteries the longitudinal smooth muscle ridge and the external elastic lamina.
Ferland-McCollough David, Slater Sadie, Richard J, Reni C, Mangialardi. G Pericytes, an overlooked player in vascular pathobiology. Pharmacol Ther. 2017; 171: 30–42.
James AW, Zhang X, Crisan M, Hardy WR, Liang P, Meyers CA, Lobo S, Lagishetty V, Childers MK, Asatrian G, Ding C, Yen YH, Zou E, Ting K, Peault B, Soo C. Isolation and characterization of canine perivascular stem/stromal cells for bone tissue engineering. PLoS One. 2017; 12(5): e0177308.
Nomina Histologica Veterinaria (https://www.eava.eu.com/veterinary-nomina-publications/)
There are a wide variety of lesions of the vessels. The general categories are Degeneration of arteries, including arteriosclerosis, atherosclerosis and arteriolosclerosis (including hyaline, hypertensive and hyperplastic changes) and Vasculitis.
The traditional meaning of vasculitis is inflammation of blood vessel walls. The difficulty comes when considering the lesions seen - many of what is seen is not vasculitis at that time, but evidence of previous vasculitis. Inflammation at some time in the course of the disease is required even if current changes are post inflammatory reactions or outcomes of previous vasculitis. Active vasculitis is when there are inflammatoy cells within or around the vessel wall with damage to the vessel wall. Damage to vessel walls results in fibrin deposition, collagen degeneration and necrosis of endothelial and smooth muscle cells. Having defined vasculitis, it is necessary to exclude some vascular lesions from the vasculitis group. Hypertension causes necrosis of the tunica media and fibrinoid change. It is not vasculitis. Thus fibrinoid and other degenerative changes do not, by themselves, indicate vasculitis.
Vasculitis results in thrombosis, ischemia and infarction.
There are many ways to separate vasculitis, and the categories or naming conventions are based on such things as vessel size (large vessel, medium vessel and small vessel), cause (septic, viral, immune mediated, idiopathic, genetic/breed related), organ or system affected (cutaneous, ear margin, localised, generalised) and outcome (infarction, ischemic dermatopathy). Thus there are many different ways of cutting the vasculitis pie.
Vasculitis by vessel type.
Vasculitis can be divided into arteritis, arteriolitis, and phlebitis. Vasculitis is seldom that simple however. In the majority of circumstances, inflammation of post capillary venules and small veins is in response to inflammatory mediators from tissue inflammation - thus a secondary 'vasculitis'. The one exception is feline infectious peritonitis where immune mediated phlebitis occurs.
Arteriolitis and arteritis is the usual primary vasculitis and the terms vasculitis, and arteriolitis and arteritis are used synonymously.
Vasculitis by vessel size
The different sizes of blood vessels can help identify the cause. While there is division into sizes, any vasculitis can involve more than one or all sizes. The naming is based on the largest vessel affected and which is affected more often.
Large vessel vasculitis (LVV) affects the large and medium sized vessels. It can affect small vessels including arterioles and venules and small veins. These are the elastic arteries and the large muscular arteries.
Medium vessel vasculitis (MVV) affects the medium sized vessels predominantly. These are the muscular arteries. It can affect small vessels too.
Small vessel vasculitis (SVV)smaller medium vessels and the small vessels. Thus small muscular arteries and arterioles. These are the intraparenchymal vessels including intraperenchymal arteries, arterioles, capilaries and venules. Medium vessels may be affected, especially the penetrating branches of the medium arteries. Cutaneous vasculitis is a small vessel vasculitis that is a Single organ vasculitis (SOV).
Variable vessel vasculitis affects any vessel without preference.
Vasculitis by aetiology
Aetiological categories of vasculitis are infectious and noninfectious.
Infectious vasculitis is the direct effect of the pathogen and the reaction to it. It can be systemic in septicemias and bacteremias, or local when it arises from inflammation in the adjacent tissue.
Noninfectious vasculitis includes the immune mediated vasculitides. Type III hypersensitivity reactions cause vasculitis when there is deposition of immune complexes in vessel walls and there is activation of complement with chemotaxis of neutrophils and necrosis of the vessel wall.
Naming of vasculitis on aetiology requires indicating the name of the primary disease.
Vasculitis by primary target
Primary vasculitis is when the particular vessel is the primary target. Idiopathic cutaneous vasculitis is an example. They can be immune complex vasculitis or not.
Seconday vasculitis is when the vessel is affected as part of a systemic disease. Infectious disease is a secondary vasculitis.
Naming of vasculitidies is further complicated by dividing the clinical disease into definable entities and the histological changes that define a type. Pathogenesis of lesions is the focus of the dermatitis patterns in dermatopathology, so this has a major effect on how we look at cutaneous vasculitis.
The skin is affected with vasculitis in 3 circumstances
- cutaneous component of systemic vasculitis
- skin limited or skin dominant of systemic vasculitis
- single organ vasculitis (SOV)
The largest vessels in the septa of the panniculis are medium sized arteries and veins. Medium vessel vasculitis is likely to produce infarcts.
Jennette JC. Overview of the 2012 revised International Chapel Hill Consensus Conference nomenclature of vasculitides. Clin Exp Nephrol. 2013; 17: 603-606.
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