Allergic Myocardial Infarction - Kounis Syndrome

Definition

Kounis syndrome is the concurrence of acute coronary syndromes with conditions associated with mast cell activation, including allergic or hypersensitivity and anaphylactic or anaphylactoid insults. It is caused by inflammatory mediators such as histamine, neutral proteases, arachidonic acid products, platelet activating factor and a variety of cytokines released during the activation process. 

In 1991, Kounis and Zavras described the syndrome of allergic angina as the concurrence of chest pain and allergic reactions, accompanied by clinical and laboratory findings of classical angina pectoris caused by inflammatory mediators released during the allergic insult. Allergic angina and allergic myocardial infarction are referred as “Kounis syndrome” .

Types

Type I variant: includes patients with normal coronary arteries without predisposing factors for coronary artery disease in whom the acute release of inflammatory mediators can induce coronary artery spasm without increase of cardiac enzymes and troponins or coronary artery spasm progressing to acute myocardial infarction with raised cardiac enzymes and troponins

Type II variant: includes patients with culprit but quiescent pre-existing atheromatous disease in whom the acute release of inflammatory mediators can induce either coronary artery spasm with normal cardiac enzymes and troponins or plaque erosion or rupture manifesting as acute myocardial infarction

Type III variant: includes patients with coronary thrombosis (including stent thrombosis) in whom aspirated thrombus specimens stained with hematoxylin-eosin and Giemsa demonstrate the presence of eosinophils and mast cells respectively.

Causes of Kounis Syndrome

Treatment

•   Steroids

•   Anti-histaminics (H1 and H2 blockers)

•   Vasodilators (NTG) and routine ACS treatment

•   Adrenaline is the drug of choice and can save lives in anaphylaxis, but in Kounis syndrome there is a chance of aggravating ischemia and worsen coronary vasospasm. Despite this risk, in severe reactions, adrenaline should be given as wide spread manifestations of Anaphylaxis are life-threatening. Sulfite free adrenaline is recommended when available. Glucagon may be considered for those who take beta blockers and do not respond to adrenaline. Fentanyl shows a slight mast cell activation as compared to morphine and should be the drug of choice when opioid analgesia is necessary.

Posted by:

              

     Lakshay Chanana

     

     Speciality Doctor

     Northwick Park Hospital

     Department of Emergency Medicine

     England

     @EMDidactic

References:

1. Kounis NG, Zavras GM. Histamine-induced coronary artery spasm: the concept of allergic angina. Br. J. Clin. Pract.45,121–128 (1991).
2. Kounis NG, Zavras GM. Allergic angina and allergic myocardial infarction. Circulation94,1789 (1996).
3. Kounis NG, Grapsas GM, Goudevenos JA. Unstable angina, allergic angina and allergic myocardial infarction. Circulation100,e156 (1999).

Angioedema - Bradykinin v/s Histamine

Angioedema
Angioedema is a Non-Pitting edema of reticular, dermal, subcutaneous and submucosal layers commonly affecting tongue, lips and upper airway (occasionally genitilia, abdomen, extremities)

Etiology

Allergic

• Mast Cell/IgE mediated - Type I hypersensitivity reaction
• Urticaria in common and a trigger is often present, acute onset
• Responds to Anaphylaxis medications

Non-Allergic 

• HAE (Hereditary Angioedema)
• AAE (Acquired Angioedema)
• Pseudo allergic 
• Idiopathic 
• ACEi related Angioedema 

Pathophys based classification
1. Histamine Mediated (Released from Mast cells or basophils)
Allergic or immunologic cause
2. Bradykinin Mediated
Hereditary or Acquired or ACE inhibitor induced edema
3. Idiopathic Angioedema 

Urticaria or Itching means histamine mediated reaction

Bradykinin affects more of deeper structures - not a/w itching but associated with pain and swelling

Presentation

Dysphagia, Change in voice, Abdominal pain, lump in throat, stridor, dyspnea 

Types:

1. Hereditary Angioedema  (HAE) - Accumulation of Bradykinin

• Autosomal Dominant (ask for family history). Can have airway or extremity swellings
• May present with recurrent abdominal pains due to mucosal swelling, urticaria is rare

1. Type I: due to C1 inhibitor (C1-INH) deficiency - increased bradykinin - 85%
2. Type II: Defective C1 inhibitor - need to test functionality 15-20%
3. Type III: due to defective factor XII (Normal levels and fiction of C1-I) - Rare

HAE often present with Erythema Marginatum - serpeginous erythematous rash but not pathognomic

• Triggers for HAE: Trauma, Medical Procedures, Stress, OCPs, Infection
• Clinical diagnosis but also show reduced C4 levels
• HAE does not respond to Anaphylaxis medications

2. Acquired Angioedema (Accumulation of Bradykinin)

Antibodies against C1 inhibitor  

AutoAb lead to reduction in C1-INH

Type 1- lymphoproliferative disorders (a/w lymphomas)

Type 2 - Autoimmune

Labs - Decreased levels of C1q (HAE - Normal C1q levels)

3. Pseudo allergic - not IgE mediated but mimics allergic AE

NSAIDs/Opioids/IV Contrast

4. Idiopathic - Unclear cause but common type of AE

All labs are normal

Chronic Urticaria can be a feature  

5. ACE inhibitor induced Angioedema - Accumulation of Bradykinin

• More prevalent in African Americans, Females, Elderly 
• ACEi interfere with bradykinin metabolism, therefore bradykinin mediated 
• Can present as "isolated genital swelling" or "peritonitic abdomen"
• Can develop with first dose or after years
• Other meds that can cause - Sitagliptin, CCBs, ARBs, Alteplase (tPA), COX inhibitors
• Patients who are on ACE inhibitor and get tPA are more likely to get tPA
• Can be unilateral as well!! (Look at the image above)
• ACEi Angioedema does not respond to Anaphylaxis medications

Recently I heard about a case where physicians did not give FFPs but intubated a patient with unilateral oral edema and also got a neck CT done. This patient was on ACEi for 6 years. FFP is a reasonable treatment option and must be considered prior to intubation. 

Consider sending a C4 level for undifferentiated angioedema (even if they are on ACEi, ACEi can unmask underlying Angioedema)

Differentials:

• Lip Abscess
• Panniculitis 
• Ludwig's Angina 

Treatment

Supportive Care

• Only a few of them require intubation
• Majority resolve with observation and treatment. AIRWAY is our concern. 
• Be concerned for potential airway compromise - Stridor, drooling, respiratory distress, change in voice 
• Be prepared for a difficult airway (Fiberoptic, Surgical)

Allergic Angioedema (Think and treat like Anaphylaxis)

• Epinephrine 0.3-0.5mg IM 1:1000
• Epinephrine drip/Steroids/Antihistaminics
• Fluids

HAE

Anaphylaxis cocktail does not help but often tried 

1) Traditional Rx - FFP (acute and chronic Rx), Antifibrinolytics (chronic), Androgens such as Danazol (chronic Rx)

Rationale for FFP: FFP contain C1-INH, other complement factors and kinin (dose 1-4 units for HAE). Few case reports mention worsening of angioedema. 

2) Newer Therapies

• C1 INH concentrates (Berinert, Cinrynze) - For acute treatment 
• Ecallantide (Plasma kallikrein inhibitors) - 30mg SQ, very expensive 
• Icatibant (Bradykinin B2 receptor antagonists) - 30mg SQ

ACEi Angioedema

• Anaphylaxis cocktail does not help but often tried 
• Discontinue ACEi
• Inconsistent data on ACEi induced Angioedema treatment 

Rationale for FFPsin ACEi Angioedema:

• FFP's supply Kininase II which functions similar to ACE and degrades bradykinin
• Inexpensive, easily available, improves symptoms
• Risks - Volume overload, ?Possible worsening of Angioedema

Admit if

• Past h/o angioedema
• Tongue/pharynx/laryngeal edema
• Lack of improvement in ED

Take Home

• Strongly consider FFPs prior to intubation in any patient with Bradykinin induced Angioedema
• Don't be surprised if Anaphylactic cocktail does not work for Bradykinin related reactions
• Get ENT/Anesthesia involved early. This is not the time to learn intubation!

References

• Temiño, Viviana M., and R. Stokes Peebles. "The spectrum and treatment of angioedema." The American journal of medicine 121.4 (2008): 282-286.
• Lewis, Lawrence M. "Angioedema: etiology, pathophysiology, current and emerging therapies." The Journal of emergency medicine 45.5 (2013): 789-796.
• Winters, Michael E., et al. "Emergency department management of patients with ACE-inhibitor angioedema." The Journal of emergency medicine 45.5 (2013): 775-780.

Author:

              

     Lakshay Chanana

     

     Speciality Doctor

     Northwick Park Hospital

     Department of Emergency Medicine

     England

     @EMDidactic

                         

Anaphylaxis - Now on the podcast !

Hi there!

Last week we dealt with anaphylaxis, now it is available on the podcast (15minutes).
This was a session which I took sometime back for the residents (The Flipped Classroom).

I still see shocked patients getting a trial of steroids/antihistaminics before epinephrine. Steroids/Antihistaminics work (if at all!) to prevent the biphasic reaction and relieve the skin symptoms.

Epinephrine is the DRUG of choice for anaphylaxis and it should be administered ASAP.

This podcast will give you an understanding about when and how to use epinephrine.

Listen to the podcast.
There is also a handout available.

Anaphylaxis Handout by Lakshay Chanana

Anaphylaxis - how are we doing?

Anaphylaxis is often one of the first emergencies which is taught to the residents. But how good are we in treating anaphylaxis - as emergency health care providers? Well, the literature says that the DOC for anaphylaxis (Epinephrine) is under-utilised, under prescribed for future use! 

Let us familiarise ourselves once again with the management of anaphylaxis, no groundbreaking information here, just a review of what we are supposed to do. 

Diagnostic criteria: Likely if any one of these criteria are met:

1. Acute onset illness with involvement of skin and/or mucosa accompanied by either respiratory compromise, falling blood pressure or end organ dysfunction. 
2. Two or more of the following symptoms occurring rapidly after exposure to the likely allergen: involvement of skin and/or mucosa, signs of respiratory compromise, falling blood pressure or end organ dysfunction and persistent GI symptoms. 
3. Falling blood pressure within minutes to several hours following exposure to a known allergen.

(Note: Do not equate anaphylaxis with hypotension/shock. Hypotension is not mandatory to administer epinephrine)

Signs and symptoms: It is primarily a clinical diagnosis. Labs are rarely helpful. 

Skin is almost always involved in about 80% of the cases. Other major systems which can be involved are: 

Skin: flushing, urticaria, angioedema, warmth, swelling, conjunctival injection

RS: Nasal congestion, Coryza, rhinorhea, sneezing, throat tightness, wheezing, SOB, cough, hoarseness of voice

CVS: dizziness, weakness, syncope, chest pain, palpitations

GI: Dysphagia, nausea and vomiting, diarrhoea, bloating, cramps

CNS: headache, dizziness, blurred vision, seizure (rare)

Management 

ABCs (Anticipate challenging airway, keep plan B ready)

O2, fluids and epinephrine

IM Epi 0.5mg 1:1000 anterolateral thigh, repeat q5-10min x 3

Adjuncts

Steroids, H1/H2 blockers, bronchodilators

For those on beta blockers : glucagon

Other vasopressors : epi, vasopressin, nor epi infusion 

Decide on admission discharge based on doses of epi required, age, comorbidities. 

Bottomline:

Know the diagnostic criteria for anaphylaxis

Don't delay epinephrine 

Hypotension is not mandatory to diagnose anaphylaxis 

Fluids, O2 and Epinephrine - treatment for anaphylaxis (not steroids and antihistaminics)

Give epi pen and educate them at discharge 

Check out the recent guidelines for more info:

https://www.aaaai.org/Aaaai/media/MediaLibrary/PDF%20Documents/Practice%20and%20Parameters/Anaphylaxis-Practice-Parameter-2014.pdf