Canine anaphylaxis Flashcards
What is anaphylaxis?
- a systemic, immediate hypersensitivity reaction that is mostly caused by IgE mediated immunologic release of mediators from mast cells and basophils
What is the best way to differentiate an anaphylactic reaction from other simpler type I HS reactions?
- characterise it as systemic HS reaction involving at least 2 organ systems (dermatologic, respiratory, cardiovascular and GI)
IgE mediated type I HS
- mast cells and basophils
- both ^ release histamine and mast cells will also release heparin
- heparin and histamine are stored in granules so there’s prompt degranulation and release from the cells
- this occurs when an antigen attaches to an IgE antibody on the surface of the cells
- the release of these granules occurs within seconds to minutes
- then within 5-30 minutes there’s downstream activation of the arachidonic acid cascade which releases prostaglandin, leukotrienes, and platelet activating factor
- about 2-6h post stimulation, there’s release of cytokines and chemokine such as interleukins and tumor necrosis factor alpha (TNFalpha)
How soon after an anaphylactic stimulus can histamine levels be measured in plasma?
- within 1 minute
What are the effects of histamine?
- cutaneous changes
- respiratory effects
- cardiovascular derangements
- GI & hepatobiliary changes
Histamine receptor activation will cause:
- vasodilation
- increased vascular permeability
- bronchoconstriction
- heart rhythm disturbances (often tachycardia)
- overall decrease in cardiac output driven by reduced cardiac contractility (inotropy)
What are the effects of heparin
- it decreases clot formation but also can be a component of a hyperfibrinolytic state meaning there’s an increase in clot breakdown
- this means the animal can form a slower and weaker clot that is more prone to rapid breakdown and an inability to stabilise the clot
Other mediators in anaphylaxis
- the arachidonic acid cascade occurs after the immediate granule release when phospholipase A2 catalyses membrane phospholipids to arachidonic acid
- arachidonic acid is then further catalysed via COV and LOX to prostaglandins, thromboxane and leukotrienes
- these are responsible for additional bronchoconstriction, pulmonary & coronary vasoconstriction, and peripheral vasodilation
- slow reacting substances of anaphylaxis SRA-A are also formed and are 1000x more potent than histamine with a longer duration of action
- these cause bronchoconstriction, permeability changes and chemotaxis
- they’re likely involved in more protracted reactions
- cytokines and chemokine are also release
- these chemotactic factors draw more immune cells to the area which causes further inflammation especially important in some of the later stage effects
What is the dogs shock organ? What is the relevance of this re anaphylaxis?
- GI & hepatobiliary system
- while there is peripheral vasodilation, alternatively there’s portal hypertension meaning there’s an increase in the blood pressure in the portal system which is the vascular bed to the GI & hepatobiliary system
- this portal hypertension occurs due to increased arterial blood flow to the portal system (hepatic arterial vasodilation) but decreased outflow of blood from the liver (increased hepatic venous outlaw obstruction
- while increasing blood flow to tissues can be beneficial, when it becomes dysregulated it is detrimental to the tissues refused causing ischaemia and damage
- when combined with the vascular permeability changes driven by heparin and the hyaocoagulability effects from the heparin the effects are compounded
Onset of allergic and anaphylactic reactions?
- often rapid within 5-30 minutes with continued rapid progression
- the time of onset and speed of progression are proportional to the severity of immunologic response so a bigger immune stimuli and mediator release will cause a quicker, more rapidly progressive and, therefore, more life-threatening response
- there are also delayed reactions and biphasic reactions which can occur
– these are often mediated by Ig other than IgE
– it is thought that biphasic reactions may increase mortality
Cutaneous presentation
- pruritus
- rhinitis
- peripheral oedema/erythema
- facial angioedema
- urticaria
These ^ are generally thought to be mediated by the H1 receptors but H2 receptors also can cause some of these.
These cutaneous signs may be a potential precursor to more severe reactions but are also often delayed or can be completely absent in rapid anaphylaxis.
Recent study showed 57.9% of dogs with anaphylaxis had no cutaneous signs reported.
When these cutaneous signs occur, they may wax and wane for days
Respiratory presentation
Cats are more likely to have respiratory signs as the lung is their shock organ.
Regardless of species the respiratory tract is affected in anaphylactic reactions in multiple ways. This can be due to pulmonary changes caused by bronchoconstriction, vasodilation, and increased vascular permeability, which causes increased airway resistance, increased fluid leak and pulmonary oedema.
There can also be increased respiratory mucus production worsening airway resistance and potentially inhibiting gas exchange. stridor or other signs of upper airway obstructive dz can occur due to laryngeal and nasopharyngeal oedema esp in pts with already compromised airway patency like breaches.
Delayed respiratory effects can also occur due to the arachidonic acid pathway and chemokine.cytokines increasing inflammatory cell recruitment, lately aggregation and damage to the pulmonary endothelium which can cause acute lung injury.
Recent study found 26.8% of dogs with anaphylaxis had respiratory signs, and respiratory distress was found to be associated with non-survival.
GI presentation
In anaphylactic reactions, the 1st signs are often severe GI signs.
Parachute GI signs including severe d+ & v+ often haemorrhagic in nature are often the presenting complaint.
These GI losses will then further contribute to hypovolaemic shock.
Vascular permeability changes and GI barrier function damage Cana also allow for bacterial and cytokine translocation and SIRS/sepsis.
Furthermore, as H2 receptors mediate gastric acid secretion, there can be significant increases in gastric acid production which can predispose these pts to gastric and duodenal ulceration.
Coagulation presentation/effects
Anaphylaxis can affect coagulation in multiple ways with severe anaphylaxis causing a global hypo coagulable state including decreased clot formation, increased clot breakdown, and decreased platelet count.
The cause of this coagulopathy is multifactorial and at this time still not fully understood, ut 1 major cause is due to the massive release of heparin.
These animals will often have a mild to severe increase in aPTT. Basically, this is due to the abundant effect of heparin on factor X activation as part of the intrinsic pathway.
Cardiovascular presentatio
One study showed CV dysfunction in 42.1% of dogs with anaphylaxis.
Hypovolaemic shock occurs due to fluid losses notably in the GIT or due to haemorrhage.
Additionally, histamine can decrease cardiac contractility and cause arrhythmias thereby dropping CO causing cariogenic shock.
Vasodilatory or maldistributive shock also occurs due to peripheral vasodilation.
There is also metabolic shock due to the cytokine effects on cell function.
These animals will often present hypotensive with other signs of severe malperfusion (dull mentation, hypothermic, elevated lactate etc) but may have pink mm.
Histamine also dampens the body’s response to catecholamines normally released in shock to thereby blocking the body’s ability to restore CO, perfusion and delivery of oxygen.
Markers of anaphylaxis
There is no anaphylaxis POC test and these dogs often don’t present with telltale cutaneous signs.
Other non-specific signs such as rapid onset severe GI signs or shock/collapse should be an indication for further investigation for markers seen in anaphylaxis.
ALT elevation and gall bladder wall oedema have been found to be markers of anaphylaxis and when combined with other findings should prompt diagnosis.
Alanine transaminase & anaphylaxis
An increase in ALT is commonly seen in anaphylaxis and often occurs very rapidly.
ALT increases due to ischaemia and hypoxia of the hepatocytes driven by alterations in blood flow as well as direct injury from cytokines to hepatocytes/
ALT will generally be high in anaphylaxis with a sensitivity of 95% and specificity of 98%.
It increases rapidly in less than 12h from insult, peaks usually in 1-2d and will often return to normal in 2-3w depending on peak value.
Gall bladder oedema & anaphylaxis
A halo or double rim effect to the gall bladder can occur almost immediately after insult due to portal hypertension and vascular permeability changes.
Sensitivity of this marker is 93% with a specificity of 98%.
Treatment options
- epinephrine
- antihistamines
- glucocorticoids
Use of epinephrine
Epinephrine is the 1st line tx for anaphylaxis. It should always be the 1st drug reached for.
Epinephrine is a mixed adrenergic receptor agonist. Among its effects, vasoconstriction increases BP and decreases airway mucosal oedema. Its positive inotropic and chronotropic effects increase CO and BP was well while its beta 2 effects cause bronchodilator. It will also suppress inflammatory mediator release by stabilising the mass cell and basophil granule release and provides relief from urticaria. It has a short duration of effects and can cause arrhythmias, hypertension, anxiety, tremors, or pallor but side effects are generally very mild esp when given IM or as a CRI.
Dose recommendation is 0.01mg/kg IM with a max dose of 0.3mg in pts <40kg or 0.5mg in pts >40kg. The dose can be repeated every 5-15mins as needed to help relieve signs. If shock or harm-abdomen is identified, then a 2nd IM dose is given before starting a CRI titrated to normalise bp starting at 0.05mcg/kg/min.
Use of antihistamines
Considered 2nd line drug in people and administration should never cause a delay of administration of epinephrine.
Although it is not a 1st line drug, blocking histamine is very important.
Since there are overlapping effects from different histamine receptors considering blocking both H1 & H2 by pairing Diphenhydramine (2.2mg/kg IM/SC/PO q8h) & famotidine (0.5-1mg/kg IM/SC/PO q12h).
Its recommended to continue antihistamine meds for 3-5d as the lasting effects of the histamine release an cause waxing and waning signs for a few days, esp the skin effects.
Use of glucocorticoids
Steroids don’t generally have direct effects on the early symptoms of anaphylaxis such ad term changes but their direct physiologic benefit in anaphylaxis is more directed in down regulating the late-stage response mediated by arachidonic acid and cytokines/chemokines or may help limit a biphasic reaction.
The onset of action is ~4-6h regardless of route.
They can be useful in animals with upper airway swelling causing obstructive changes.
Anaphylactic haemoabdomen
Pts usually with the worst morbidity and mortality are those with severe haemoabdomen.
Portal hypertension, vascular permeability alterations and coagulopathy can lead to intra-abdominal bleeding.
Rapid administration of epinephrine along with plasma transfusion.
These dogs often rapidly stabilise after epinephrine and plasma, but some need a larger volume of plasma, red blood cells, platelets, or fresh whole blood transfusions and prolonged epinephrine CRI to stabilise.
Mass like haematomas have been reported on US esp in the liver due to intraparenchymal bleeding.
Other tx
General care for shock including IVFT, epinephrine CRI as needed, or dobutamine is there is continued hypotension and evidence of poor inotropy.
Monitoring and correction of cardiac arrhythmias may be necessary.
GI support is also important e.g. NGT
