Vasculopathies and Veterinary Dermatology

Introduction

Strictly speaking, vasculitis can only be considered when the following criteria are observed:
a) endothelial cell hyperplasia
b) thickening of the vascular wall
c) leukocyte infiltrate
d) extravasation

In reality, the concept of vasculopathy has evolved significantly, and subtle vascular changes have been described in numerous dermatopathies.
The question to ask is whether to speak of vasculopathies or vasculitis.

Anatomical Reminder

The cutaneous vascular system is dense and complex. It is organized into three levels:
e) superficial intradermal vascular plexus
f) deep intradermal vascular plexus
g) subcutaneous vascular plexus.

The three vascular plexuses are interconnected, though with significant variations depending on the species and cutaneous regions.
Generally, small arterioles branch vertically from the dermal plexus and give rise to a vascular arborization around the hair follicles. This vascular system also drains the adnexal glands, sebaceous and apocrine sweat glands. Sometimes, the irrigation of apocrine glands occurs via arterioles directly from the subcutaneous plexus.
From the superficial plexus, a network of small arterioles, rich in anastomoses, forms a capillary network connected to post-capillary venules.
In humans, arterio-venous shunts exist. These shunts are involved in thermoregulation. These shunts are not described in veterinary medicine.
The dermatological symptomatology of vasculopathies is directly related to the type of damaged vessels. Generally, involvement of small vessels, arterioles, venules, or capillary networks will lead to localized lesions such as purpura, hemorrhagic bulla, crust, ulcer, or necrosis. Involvement of larger vessels (small arteries) will result in more extensive lesions, regional necrosis, or nodule formation (in humans).

Classification

The classification of vasculopathies in animals is still very uncertain. Several classifications are possible:

1° Infectious vasculopathy: bacterial, mycobacterial, Rickettsial, viral, fungal, protozoal, helminthic…

2° Non-infectious vasculopathy:

• a) exogenous cause: drug-induced, post-vaccinal, food-related (additives…) …
• b) endogenous cause: neoplasia, secondary to a systemic disease: plasmacytic pododermatitis, lupus, dermatomyositis…
• c) idiopathic

3° Non-immunological vasculopathy: inflammation not directly directed at the vascular wall:

• h) microbial vasculitis
• i) neoplastic vasculitis
• j) toxic vasculitis
• k) vasculitis due to hemodynamic changes

4° Immunological vasculopathy: immune-mediated mechanism directed against a component of the vascular walls.
Histologically, vasculitis can be classified as (see Kirk Muller).

1. Neutrophilic vasculitis
2. Eosinophilic vasculitis
3. Lymphocytic vasculitis
4. Granulomatous vasculitis
5. “Mixed” vasculitis
6. “Cell-poor” vasculitis

Infectious Vasculopathies

The observed symptomatology depends on the importance of the pathological process and the involvement of target organs.
In some cases, the condition can be systemic. General signs such as fever, severe lethargy, myalgia and arthralgia, ptyalism, lymphadenopathy, and even epistaxis may be noted. Functional signs related to affected organs may appear (hepatic, renal failure…).
In other cases, vasculopathy will be limited to cutaneous involvement without general signs.
On the skin, ecchymoses or even cutaneous hemorrhages, pustule formation, bullae, and necrosis with ulcer will be noted.
During deeper involvement (subcutaneous), nodules may be observed.
The body regions most susceptible to vasculopathies are the extremities, paw pads, ear pinnae, lips, tail tip, scrotum…

“Paraneoplastic” Vasculopathy – Toxic/Drug-Induced Vasculopathy

Vascular lesions during toxic/drug reactions are most often subtle (non-leukocytoclastic). The inflammatory component is strong with perivascular edema formation and erythrocyte extravasation.
The etiopathogenic process remains uncertain. It seems that drugs or metabolites could act as haptens inducing immunoglobulin and complement deposits in the vascular walls.

Hemodynamic Vasculopathy

• Thromboembolism from cryoglobulin/cryofibrinogen or idiopathic
• Arteriovenous shunt: bypass of the capillary network with secondary ischemic necrosis.

Immunological Vasculopathies

The presumed mechanism of action is most often a type III hypersensitivity reaction (immune complex deposits) or even type II???

a) Post-vaccinal Vasculopathy

While certain vaccinations can clearly induce vasculitis, the consensus regarding etiopathogenesis remains unclear.
Indeed, this disease seems to be more common in the USA. It has been suggested that the cause of more frequent vascular reactions in North America may be related to the use of different vaccines, consisting of attenuated strains. Furthermore, vaccination protocols of American and European veterinarians differ (American veterinarians most often vaccinate with “all in one” vaccines, including rabies).
Nevertheless, this entity is characterized by the appearance of a local reaction and/or distant lesions (ear tips, tail tip, bony prominences, paw pads) within weeks or even months following vaccination.
Small dogs would be more exposed: Chihuahua, terriers, dachshunds, Bichon, Shetland…

b) Ear Tip Vasculopathy

This syndrome should be considered a clinical presentation and not a disease. Indeed, several causes can be implicated:

• Vaccine-induced vasculopathy
• Cryoglobulin or cryofibrinogen vasculopathy
• Familial vasculopathy of Jack Russell, German Shepherd

c) Genetic Vasculopathy

• In German Shepherds
  The condition most often begins between 4 and 10 weeks of age, 7 to 10 days after vaccination. Dogs are lethargic, feverish, and sometimes exhibit generalized lymphadenopathy. Swelling of the nasal planum is noted with crusts or ulcers. Lesions extend to the ears and tail tip. Paw pads can be swollen and dépigmented to varying degrees.
  Histologically, a mixed vascular involvement, venules and capillaries, as well as collagenolysis are observed.
  Spontaneous healing is usually observed.
  A genetic susceptibility (autosomal recessive) is suspected.
• In Greyhound Dogs
  The condition begins between 6 and 72 months of age.
  Cutaneous swelling followed by deep, well-demarcated ulceration (from 1 mm to 10 cm) is observed on the tarsus, knees, inner thighs, and more rarely on the forelimbs.
  In 25% of cases, these skin lesions are associated with renal involvement.
  Histology shows thrombosis of arterioles, venules, or capillaries.
  These abnormalities are believed to be caused by bacterial toxins (Coliforms contaminating food) affecting genetically “sensitive” dogs.
• In Jack Russells
  The condition most often begins before 1 year of age, very often 2 to 3 weeks after vaccination. Well-localized alopecias with crusts and ulcerations are noted on the bony prominences of the skull and extremities, as well as on the ear borders. Lesions may sometimes be noted on the paw pads.
  Genetic susceptibility is suspected.

d) Lupus Vasculopathy

e) Vasculopathy and Toxicodermia

f) Vasculopathy associated with food HS/atopic/insect bites

g) Vasculopathy associated with cold and exertion

• In sled dogs, an ischemic vasculitis of the paw pads induced by cold is described. The lesions would be consecutive to the excessive production of an arachidonic acid metabolite, thromboxane A2 (TxA2). TxA2 is a potent vasoconstrictor that also induces platelet aggregation. A reduction in blood flow in peripheral tissues such as the paw pads is observed. Platelet aggregation inducing thrombus formation would worsen tissue ischemia. In some severe cases, death by collapse can be observed.