M.H.

H ALSHAMRY

HypersensItIvIty
► Types :

Type I Type II Type III Type IV

Anaphylactic cytotoxic reactions - Immune complex reactions Delayed type reactions -cell mediated
Name
Allergic - Immediate Autoimmune reactions ( ICS )
type

Timing Immediate ( mins to hrs ) 6 - 18 hrs. > 18 hrs up to 24, 36 hrs 2 - 3 days

Antibody
IgE IgG or IgM Only IgG No antibody
Responsible
Tissue antigen as Chronic Ag as HBV ,
Antigens IgE parietal cells , RBCs HCV - cellular Ag intracellular antigen
skin , thyroid

Activated macrophages & T helper

Cell
Mast cells & Basophils NK cells Neutrophils cells ( special forms DTH- delayed
Responsible
T hypersensitivity )

Neutrophils mediators
Preformed : Histamine.
Polymorph nuclear l
Newly formed : Gamma interferons activates
eukocyte mediators : -
Mediators leukotrienes , complement mediators macrophages & T helpers
1 - Azurophil (acidic catharsis)
prostaglandins ,
2 - specific as collagenase ,
cytokines. elastase
Skin reaction according to layer of
skin affected
1 - Epidermal ( superficial layer ) →
contact dermatitis as in
watches & rings
Skin Test Prick test No skin test Arthus reaction 2 - Deep layer of epidermis & dermis
cutaneous basophile hyperplasia (CBH)
3 - Deep layer of dermis →
tuberculin test
4 - Subcutaneous as in Kveim test
in sarcoidosis

Avoidance According to affecting organism :

TTT Antihistamine Steroids plasmapheresis Steroids Anticytokines ex. antitubercular drugs for T.B.
Anti allergic

⋆ Thyroid causing
Hashimoto’s &
⋆ Anaphylaxis hyperthyroidism. ⋆ Glomerulonephritis ⋆ Mycobacterium TB Mycobacterium
⋆ RH incompatibility. ⋆ Hepatitis B, C leprosy Trypanosome leishmania
⋆ bronchial asthma
⋆ Autoimmune hepatitis. ⋆ collagen disorders : as Intracellular virus & intracellular
Examples ⋆ eczema
⋆ Autoimmune SLE & rheumatoid arthritis bacteria as listeria monocytogenes
⋆ allergic rhinitis hemolytic anemia.
⋆ Contact Dermatitis
⋆ Autoimmune skin
⋆ Food Allergy ⋆ D.M Type I
manifestation
" bullous skin reaction ". ⋆ M.S

N.B. there is a new type of hypersensitivity which is called “ Type V ”, which is a subtype of Type II the only
difference between them is that Type II causes tissue damage while in Type V there are auto Abs that cause
stimulation or overactivity instead of causing damage. Ex :
1 - Anti TSH receptor : causing graves' disease.
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2 - Anti Glomerular basement membrane : causing good pasture syndrome.

3 - Anti body against acetylcholine receptors causing Myasthenia graves.
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Anaphylaxis
► Definition :

⋆ It is the most serious & potentially acute life threating condition due to massive release of pharmacological
mediators inside granules , from both mast cell & basophile to circulation following exposure to allergen.
NB. patient with asthma only : dissociation of granules contents as histamine , Leukotrienes are release from granule
through granule membrane to circulation , but in other type of anaphylaxis granules itself reach the circulation

► Etiology : ( Ig mediated & Non - Ig mediated )

I - Ig mediated :
⋆ The patient exposed to the allergen ➔ no effects but the patient’s body will start making antibodies ( IgE )
➔ second exposure to the same allergen ➔ anaphylaxis

II - Non - Ig mediated : = ( anaphylactoid reactions ) = chronic recurrent

1 - Immunocomplex : as drugs & opioids ( opioids have direct effect on mast cells )

2 - complement mediated : as by contrast media or blood products

3 - Without known mechanism : as in cyclic anaphylaxis ( female allergic to her own hormones & when
menses anaphylaxis occurs ) & NSAIDs.

4 - Food mediated - exercise precipitated :

⋆ eating certain food such as green apple then exercising causes anaphylaxis.

N.B. Perioperative anaphylaxis : allergy from latex gloves.

► Clinical picture : -

⋆ symptoms & signs typically occur within 30 minutes of initial exposure but may appear up to several
hours later. These include ( in order of frequency ) :

1 - Skin manifestations , typically urticaria but also flushing , blotchy rashes & pruritus especially in
palms & soles.

2 - Respiratory distress , including wheezing , stridor, bronchospasm & airway angioedema differentiate it
from urticaria that urticaria is hot , red with blotches but the angioedema is in tight spaces , pale & itchy.

3 - Gastrointestinal symptoms , including cramping , emesis & diarrhea ( especially in food allergy ).

4 - Hypotension , often manifested as lightheadedness , dizziness or syncope.

√ The condition is potentially fatal , especially if untreated & can affect both nonatopic & atopic persons.
√ serious anaphylaxis : patient takes B blockers: bradycardia or take food esp. peanut.
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► D.D of anaphylactic shock :

1 - Vasovagal attack ( no urticaria , bradycardia & no sweating )

2 - Acute Pulmonary embolism
3 - Acute MI
4 - fatal Arrhythmia ( ventricular fibrillation , atrial fibrillation )
5 - Panic disorder
6 - scombroid fish toxicity : as defreezing of decomposed fish containing extremely high amount of histamine.

N.B. 1 - No anaphylaxis without urticaria.

2 - Anaphylactic shock only if accompanied by hypotension.

► Laboratory diagnosis : -

1 - Anaphylaxis is mainly diagnosed from C/P & history of the causes as " drugs , host , food "

2 - First thing to be elevated is plasma histamine then serum tryptase enzyme from mast cell , may
be detected shortly after a reaction providing support to the diagnosis.

3 - Specific IgE serum or skin testing may be performed to suspected allergens. Skin testing , which is
usually more sensitive , optimally occurs a weeks after a severe reaction to avoid falsely negative
testing during a post-reaction “ refractory period ”.

4 - Also , there's high IGE & eosinophilia.

► Treatment :

♦ remove causative - ABC " air way , breathing , circulation "

1 - Lifesaving & the cornerstone factor drug is Epinepherine 0.3 - 0.5 IM Given in front of the thigh ( best
site for absorption ) ** Don't give it IV **

2 - Supportive therapy iv fluids , plasma expanders , oxygen , maintain airways , warming…

3 - Steroids as hydrocortisone for delayed or chronic intercurrent or chronic recurrent not for
immediate reaction.

4 - Old generation antihistaminic drugs or old generation H2 blockers maybe used.

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Food Allergy
► Types of reactions to food :

I - Toxic : d.t contamination from toxic material such as mercury or organophosphorus or from bacterial
infections as staph.

II - Non - toxic :
A - Immune : 1 - IgE mediated.
2 - Non - IgE mediated : as celiac disease.
3 – mixed : as dermatitis herpetiformis
B - non - immune : may be d.t :
1 - High content of vasoactive amines such as Rickford cheese & scombroid fish & people
taking high too much caffeine.
2 - Congenital enzymatic deficiency as lactase or sucrase defiance

True food allergy

► Def. : Immediate allergic reactions within 2 hrs of ingestion of foods which are much less common
among adults than children.

► Etiology :

⋆ Most acute systemic food allergy is caused by proteins in milk , egg, wheat , soy , fish , shellfish peanuts & tree nuts.
⋆ Milk & egg allergies in atopic children are often outgrown by adulthood.
⋆ Shellfish , peanuts & tree nuts cann`t be outgrown so they are most common causes of food anaphylaxis in adults.

► Diagnosis :

⋆ Diagnosis of food allergy relies on a combination of history , skin tests & serum specific IgE tests. There is no
role for specific IgG testing for evaluating food hypersensitivity.
⋆ Because of frequent false - positive IgE tests , especially among atopic patients , oral food challenge remains
the gold standard for diagnosis. However , this procedure , should only be conducted by an experienced
provider in a well - equipped setting.

► Management :

⋆ involves strict avoidance of the culprit food & guaranteed access to self - administered epinephrine.
⋆ Other IgE - mediated food reactions :
1 - Oral allergy syndrome ( also known as pollen - associated food allergy syndrome ) :
√ is the result of cross - reactivity between food & pollen proteins. Affected individuals have known seasonal
pollen allergies ( most commonly tree pollens ) & experience itching of the oral mucosa upon ingestion of
certain raw fruits & vegetables. In contrast to systemic food allergy , symptoms are limited to the
oropharynx & usually do not involve other organ systems or progress to anaphylaxis.

2 - Alpha gal ( galactose alpha 13 - galactose ) :

√ is a carbohydrate found in red mammalian meats , including. beef, pork & lamb ; but not - in human tissues.
Sensitization to this epitope has been linked to tick bites , so nonatopic individuals are at risk In contrast to
conventional systemic food allergy , the reaction to red meat typically occurs 4 - 6 hrs after ingestion.
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Red Man Syndrome

⋆ Like radiocontrast media reactions , the " red man syndrome " results in anaphylactoid symptoms ,
especially flushing , pruritus & erythema of the upper body.

⋆ Initially described as a vancomycin - infusion reaction , it can also occur after intravenous infusion of
opioids but still more common in vancomycin intake.

⋆ The reaction is related to the rate not the type of vancomycin or opiod of drug administration resulting
in direct activation of mast cells.

► Management :

1 - administration of an antihistamine such as diphenhydramine , 25 - 50 mg intravenously or

intramuscularly & reinitiating the vancomycin infusion at no. more than half the former rate.
2 - In patients who have previously experienced a vancomycin infusion reaction , premedication with an
H1 - antagonist ( e.g. diphenhydramine ) & H2 - antagonist ( e.g. cimetidine ) is recommended 1 hour
prior to the infusion.
3 - Although rare, IgE sensitization to vancomycin does occur & should be suspected in patients who
have received multiple courses of the drug.
4 - Skin testing is helpful because vancomycin , as a " complete allergen " can elicit positive skin tests.
5 - Desensitization to vancomycin is possible for patients with positive skin tests & no acceptable
alternative antibiotic.

N.B. Drug desensitization can be done in : 1 - Aspirin 2 - Insulin 3 - Vancomycin

HLA Haplotypes & Risk of delayed onset drug hypersensitivity syndrome

⋆ Activated cytotoxic CD8 T lymphocytes play a key role in the pathogenesis of serious , drug - induced
adverse cutaneous reactions , such as toxic epidermal necrolysis.
⋆ There are striking , medication - specific associations between inheritance of particular HLA - B alleles
& risk of these hypersensitivity reactions in defined populations ( mostly South Koreans ).

◊ Most notably :

√ B * 57 : 01 confers risk for reactions to abacavir.

√ B * 15 : 02 for carbamazepine.
√ B * 58 : 01 for allopurinol.
√ B * 13 : 01 for dapsone ( used in leprosy & other skin problems ).

⋆ The most likely mechanism is a direct interaction between the drug & the antigen - binding cleft of
the HLA - B molecule , such that many " self " antigens subsequently bound by the HLA - B molecule are
perceived as " foreign " eliciting massive CD8 T - cell activation.

⋆ Current FDA recommendations call for testing for the relevant FLA - B allele prior to initiating therapy
with these drugs in all patients from Asian descents.
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Mast cell acti vation syndrome ( M CAS )

⋆ Associated with repeated anaphylaxis.
⋆ It is idiopathic.
⋆ Its molecular cause is mutation of mast cell growth receptor ( KIT ) , the patients are negative for
KIT D816V. ( V is for valine which is replacing the original amino acid ).

► Diagnosis :
⋆ Serum Tryptase enzyme
⋆ Serum leukotriene B 4
⋆ Prostaglandin F 2 alpha
⋆ Urinary N - methyl histamine
⋆ Serum histamine
⋆ rinary leukotriene E 4

► Treatment :
⋆ Old generation antihistaminics.
⋆ Aspirin : can reduce flushing.
⋆ orticosteroids.
⋆ Omalizumab as monoclonal antibodies.
⋆ Anti - asthmatics.

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