hsn reaction

1. HYPERSENSITIVITY REACTIONS
Guided By: Dr Madan N
Presented By: Sanskriti Shah

2. CONTENTS
 Definition
 Classification
 Type I hypersensitivity reactions – Pathophysiology, Etiology,
Management
 Type II hypersensitivity reactions – Pathophysiology, Etiology,
Management
 Type III hypersensitivity reactions – Pathophysiology, Etiology,
Management
 Type IV hypersensitivity reactions – Pathophysiology, Etiology,
Management
 Type V hypersensitivity reactions

3. Hypersensitivity reaction
Hypersensitivity refers to a condition in which immune response results in
excessive reactions leading to tissue damage, disease or even death in the
sensitised host.

4. • Hypersensitivity reactions are classified into two main types,
'immediate' and 'delayed' types based on the time required by
sensitized host to develop clinical reactions upon exposure to the
shocking dose of the antigen.
CLASSIFICATION

5. CLASSIFICATION
Type I. Anaphylactic Type
Type II. Cytotoxic Type
Type III. Immune Complex-Mediated
Type IV. Cell-Mediated
Type V. Stimulatory Reactions

6. Type I. Immediate Hypersensitivity Reactions
PATHOGENESIS
i) During first contact of the host with the antigen, sensitisation takes place.
circulating B lymphocytes get activated and differentiate to form IgE-secreting plasma
cells.
IgE antibodies so formed bind to the Fc receptors present in plenty on the surface of
mast cells and basophils,
Thus, these cells are now fully sensitised for the next event.
ii) During the second contact with the same antigen, IgE antibodies on the surface of
mast cells-basophils are so firmly bound to Fc receptors that it sets in cell damage—
membrane lysis, and degranulation of mast cells-basophils.
iii) The released granules contain important chemicals and enzymes with
proinflammatory properties— histamine, serotonin, chemo tactic factors of anaphylaxis
for neutrophils and eosinophils, leukotrienes B4 and C4, prostaglandins (thromboxane
A2, prostaglandin D2 and E2) and platelet activating factor

8. PRIMARY MEDIATORS
 Histamine - causes vasodilation, increased capillary permeability and
contraction of smooth muscles.
 Serotonin - causes vasoconstriction, increased capillary permeability and
contraction of smooth muscles.
 Eosinophil chemotactic factor – released from mast cells granules and are
strongly chaemotactic for eosinophils. These probably contribute to the
eosinophilia associated with many hypersensitivity reactions.

9. Secondary mediators
 Slow reacting substance of anaphylaxis (SRS-A) – much more potent bronchoconstrictors than
histamine.
 Prostaglandin and thromboxane
 Paf

11. Etiology
 Allergic reactions
Reactions can be elicited by various aeroallergens (eg, pollen, animal
dander), drugs, or insect stings.
 Other possible causes are latex, drug, and food allergy.

12.  Allergens
 Allergens can be complete protein antigens or low–molecular- weight proteins
capable of eliciting an IgE response.
 Pollen and animal dander represent complete protein antigens.
 Haptens are low–molecular-weight (inorganic) antigens that are not capable of
eliciting an allergic response by themselves.
 must bind to serum or tissue proteins in order to elicit a response.
 a typical cause of drug hypersensitivity reactions.

13.  Foods
 most common food allergens are
 peanuts, tree nuts, finned fish, shellfish, eggs, milk, soy, and wheat.
 Certain foods can cross-react with latex allergens.
 These foods include banana, kiwi, chestnut, avocado,
pineapple, passion fruit, apricot, and grape.
 Hymenoptera
 Bee, wasp, yellow jacket, hornet, and fire ant stings
can cause IgE-mediated reactions.

14. SIGNS AND SYMPTOMS
Systemic reaction
 usually IV injection of an antigen to which the host has already
become sensitized
 state of shock can be produced within minutes (may be fatal)
also also called anaphylaxis
 .

15. Local reactions
Depend on the portal of entry of the allergen. May take the form of:
 localized cutaneous swelling (skin allergy, hives)
 Conjunctival discharge (conjunctivitis)
 hay fever (allergic rhinitis)
 bronchial asthma
 allergic gastroenteritis (food allergy)

16. DIAGNOSTIC TESTS
• CBC
– Increased WBC – eosinophil
count
• Increased serum IgE levels
– Normal values 100-200IU/ml
– Does not determine indicate specific
antigen
• Radioallergosorbent Test
(RAST)
– Determines the blood concentration of
IgE directed against a specific antigen
and thus can determine specific antigen

17. OTHER TESTS
 Scratch test
 Intradermal test
 Oral food challenge
 In vitro testing

18. Scratch Test
 A test for allergy performed by scratching or
pricking the skin and applying an allergen to the
wound
 localized reaction (wheal- red raised area) when the
test result is positive
 Results in an immediate hypersensitivity reaction to an
allergen
 Discontinue antihistamines for 5 days before the test
 Serious reactions are rare

19. Intra dermal Skin test
 The allergens are either injected intradermally or into small scratchings
made into the patient's skin
 If the patient is allergic to the substance, then a visible inflammatory reaction will
usually occur within 30 minutes.
 This response will range from slight reddening of the skin to full-blown hives in
extremely sensitive patients.
 Problems: some people may display a delayed-type hypersensitivity (DTH) reaction
which can occur as far as 6 hours after application of the allergen and last up to 24
hours. This can also cause serious long-lasting tissue damage to the affected area.
These types of serious reactions are quite rare.

21. Oral Food Challenge
 Effective for some individuals in identifying specific food
allergens when skin testing has been inconclusive
 Eliminate suspected foods for 7-14 days before testing
 Incremental doses of the food are given to the patient starting
with a very small quantity. Each dose is followed by a period of
observation and assessment prior to receiving the next dose.
After receiving the final dose, the patient undergoes an additional
observation period and final assessment.

22. In Vitro Testing
• Drawing blood from a client and
exposing it to different panels
containing food and mold allergens
• After incubation the cells are
checked
• Positive reaction
– Increase WBC size by 12 %
– Increased platelet
aggregation

23. MANAGEMANT
Decongestants
 vasoconstriction in the inflamed tissue thereby
reducing the edema
 Caution in patients with HPN, glaucoma
Antihistamines
 blocks histamine from binding with its receptor preventing
vasodilation and capillary permeability
 Sedation

24. Corticosteroids
 decrease inflammation by preventing the synthesis of
mediators
 Nasal
 Beclomethasone
 Fluticasone
 Oral
 Prednisolone
 Prednisone

25. Mast Cell Stabilizers
 Prevent mast cell membranes from opening when
allergen binds to IgE
 Cromolyn sodium
Leukotriene Inhibitors
 Zileuton
 Zafirlukast

26. 26
Management
Epinephrine is the first line treatment of anaphylaxis, and delayed administration increases the
likelihood of poor outcomes
In most situations intramuscular administration is preferred, but IV epinephrine can be used in
the ICU. IM epinephrine should be given in 0.2–0.5 mg doses (1:1000 dilution), and repeated
every 5 min depending on the resolution of symptoms
26
Patients should be placed on pulse oximeter and given high flow oxygen as needed.
Patients in anaphylactic shock should be placed in supine or Trendelenburg position to increase
blood return to the heart.
Due to the intravascular depletion, fluid is often necessary to maintain pressure.
Crystalloids or colloids may be used, but should be aware of the anaphylactic potential of some
colloid solutions. Normal saline (0.9% saline) should be chosen over other crystalloids as it
remains in the intravascular space longer than dextrose solutions.

27. Epipen

28. 28
Adjunct treatments
1. H1-Antihistamine
2. H2-Antihistamine
3. Bronchodilator
4. Glucocorticoids

29. 29

30. Desensitization
 The most common form of desensitization involves
subcutaneous injections of small amount of the allergen
 An increasing dose is usually given weekly until the patient is
receiving a 0.5ml dose
 Recommended course of treatment is approximately 5
years
 Instead of IgE , IgG is produced and binds with the allergens so as
not to cause degranulation of mast cells or basophils.

31.  Desensitization has been effective for a few antigens, particularly bee
venom.
 This treatment can have 2 effects:
 T-helper 1 cells produce more IgG which binds to the antigen so that it
can’t bind to IgE receptors on mast cells and cause release of
histamines.
 IgG binds to and removes the antigen before it binds to T-helper 2
cells. The T- helper 2 cells will then not be able to produce the B cells
that will produce IgE.

32. Allergic rhinoconjunctivitis s/s
 Congestion
 Sneezing
 Itchy , runny nose and eyes;
 Itching of the palate and inner ear.
 postnasal drip, which can cause sore throat,
coughing, or throat clearing.

33. Rhinoconjunctivitis
 usually results from exposure to aeroallergens
 can be seasonal or perennial.
 Airborne allergens typically also cause ocular symptoms
consisting of itchy eyes, tearing, swelling or redness of the
eyes.
 Repeated exposure to the allergen can result in chronic allergic
inflammation, which causes chronic nasal congestion that can
be further complicated by sinusitis.

34. s/s
 Patients may sneeze, be congested, have a runny nose, or
have frequent throat clearing and/or cough from postnasal drip.
 Sclera may be injected, and patients may have dark rings
under the eyes (ie, allergic shiners).
 Nasal mucosa can be boggy and pale, usually with clear
drainage.
 The pharynx may have a cobblestone appearance reflecting
lymphoid hyperplasia from postnasal mucus drainage.
 The patient may have frontal or maxillary sinus tenderness
from chronic sinus congestion or infection.

35. allergic shiners

36. Additional Diagnostic test
 Nasal smear tests
 look for eosinophils.
 However, regular use of a nasal corticosteroid can lower
the eosinophil count.
 Elevated eosinophil levels can be consistent with allergic
rhinitis.

37. MANAGEMENT
 Avoid the offending allergen, if possible.
 Oral H1-receptor blockers
 helpful for controlling itchiness, rhinorrhea, and lacrimation
but most have little effect on nasal congestion.
 intranasal glucocorticosteroid
 control nasal symptoms, including nasal congestion.
 need to be used regularly to be effective
 patients may need to use them for a week or more before
maximum effect is seen.

38.  Other topical nasal agents include
 azelastine
 olopatadine (H1-receptor blockers)
 cromolyn (a mast cell stabilizer).
 Nasal antihistamines have a rapid onset of action and can be
used on an as-needed basis.
 Topical nasal decongestants can provide immediate relief of
nasal congestion and can be used temporarily and as needed.
 Note: Patients should be cautioned not to use them for more
than a few days, however, as they can cause rebound
congestion (rhinitis medicamentosa).

39.  ocular symptoms
 Topical decongestants, mast cell stabilizers, or
antihistamines
 artificial tears - can be refrigerated for an extra cooling
effect.
 Cold compresses can also be used.
 Note: use of topical decongestants should be limited to a
few days, as longer use can result in rebound
vasodilation.

40. Antigen-injection immunotherapy
 AKA: subcutaneous immunotherapy (SCIT)
 very effective in treating inhalant allergies and can be considered in patients
whose symptoms do not respond well to medications or in patients who
cannot avoid the allergen in question.
 The mechanism of action of immunotherapy is not yet fully elucidated.

41. Sublingual/swallow immunotherapy (SLIT)
 An alternative to antigen-injection immunotherapy
 involves having the patient hold extract under the tongue for 1-3
minutes before swallowing.
 It offers the advantage of a lower likelihood of systemic adverse
effects and has been shown to reduce allergic rhinitis and asthma
symptoms.
 may have a more significant impact on these symptoms
than SLIT.
 still being evaluated for FDA approval

42. Allergic asthma s/s
 Bronchoconstriction
 shortness of breath, wheezing, cough, and/or chest tightness.
Cyanosis of the lips, fingers, or toes (caused by hypoxemia)
may occur with severe asthma.
 Long-term allergen exposure can cause
 chronic changes of increased difficulty breathing and
 chest tightness

43. Additional diagnostic tests
 Spirometry/pulmonary function tests
 Spirometry or pulmonary function tests offer an objective means of assessing
asthma.
 Peak-flow meters can also be used for this and can be used by patients at
home to monitor their status.
 Induced sputum:
 Sputum induced from the airways can be evaluated for eosinophils, which is
a measure of inflammation seen in asthma.

44. MANAGEMENT
 Avoid the offending allergen, if possible.
 Therapy depends on the severity of disease.
 albuterol metered-dose inhaler (MDI) (or nebulizers for young children)
to use as needed.
 Inhaled glucocorticosteroids should be added if appropriate.
 In general, these medications are used if symptoms occur more
than twice weekly or if abnormal spirometry findings reverse with
the inhalation of a short-acting bronchodilator.
 .

45.  Leukotriene inhibitors can also be added.
 Systemic corticosteroid bursts may need to be used
for exacerbations of severe cases.
 Patients with allergic asthma may respond well to
specific allergen immunotherapy.

46. Urticaria/angioedema
s/s
 Diffuse hives or wheals may occur and cause significant pruritus;
 individual wheals resolve after minutes to hours, but new wheals can continue
to form.
 Acute urticaria (lasting < 6 wk) can be caused by viral infections, foods,
drugs, or contact allergens.
 Chronic urticaria lasts longer than 6 weeks. Although many causes are possible,
often, a cause is not found. In many cases, this is not due to antigen-IgE –
mediated immediate hypersensitivity but to an autoantibody to the high affinity
IgE receptor or to IgE itself.

47.  (+) wheals with surrounding erythema.
 Wheals from allergic causes usually last a few
minutes to a few hours.
 Wheals due to cutaneous vasculitis may last more than 24 hours and may
leave postinflammatory hyperpigmentation upon healing.

48.  Angioedema
 is localized tissue swelling that can occur in soft
tissues throughout the body.
 pain at the site of swelling instead of pruritus, which occurs with
urticaria.
 particularly concerning if pharyngeal or laryngeal tissues are
involved.
 Angioedema of the laryngopharynx
 can obstruct the airway; difficulty breathing.
 Stridor or hoarseness
 can be life threatening.

49. MANAGEMENT
 Avoid the offending allergen if known.
 H1-receptor blocker should be added.
 If symptoms are not controlled with this alone,
 an H2-receptor blocker, leukotriene inhibitor, or oral
glucocorticosteroid can be added.
 Most patients require higher than the usual doses;
 employing twice daily H1 and H2 antihistamines for
successful control is not uncommon.

50. Anaphylactoid reactions
 Non–IgE-mediated mast cell and basophil degranulation can
occur from a variety of substances.
 Due to complement system activation
 The clinical manifestations can appear the same.
 Causes can include
 radiocontrast dye, opiates, and vancomycin (eg, red man
syndrome).

51. Latex Allergy

52.  Avoid products containing latex (surgical gloves,
tubings, condoms etc.)
 Other interventions similar to hypersensitivity
reactions
 Use synthetic substances that do not contain
latex protein
 ElastyLite gloves;etc

53. Type II. Cytotoxic Type
 Body makes special autoantibodies directed against self-
cells (antigens present on the surface of cells or other tissue
components)
 antigen:
 1. may be intrinsic to the cell membrane
 2. may take the form of an exogenous antigen adsorbed on the
cell surface.
 hypersensitivity results from the binding of antibodies to
normal or altered cell-surface antigens

54. PATHOGENESIS
i) The antigen on the surface of target cell (foreign cell) attracts and binds
Fab portion of the antibody (IgG or IgM) forming antigen-antibody
complex.
ii) The unattached Fc fragment of antibodies (IgG or IgM) forms a link
between the antigen and complement.
iii) The antigen-antibody binding with Fc forming a link causes activation of
classical pathway of serum complement which generates activated
complement component, C3b, by splitting C4 and C2 by C1.
iv) Activated C3b bound to the target cell acts as an opsonin and attracts
phagocytes to the site of cell injury and initiates phagocytosis.
v) Antigen-antibody complex also activates complement system and
exposes membrane attack complex (MAC) that attacks and destroys the
target cell

55. Type II examples
1. Transfusion reactions
 cells from an incompatible donor react w/ the host’s antibody
2. Erythroblastosis fetalis
 there is an antigenic difference between the mother & the fetus,
and antibodies (IgG) cross the placenta & cause destruction of
fetal red cells.
3. Autoimmune hemolytic anemia, agranulocytosis,
throbocytopenia
 individuals produce antibodies to their own blood cells, w/c are
then destroyed.
 4. Drug reactions
 antibodies are produced that react w/ the drug.

56. Type II hypersensitivity – immune-mediated
destruction of red blood cells
Drug (p=penicillin)
modified red blood cells
induce the production of
antibodies, because the
bound drug makes them
look foreign to the
immune system. When
these antibodies are
bound to them, the red
blood cells are more
susceptible to lysis or
phagocytosis. Onset is
dependent on the
presence of specific
antibodies.

57. Collaborative Management
 Discontinue the offending agent
 Plasmapheresis
 Filtration of the plasma to remove specific substances like
autoantibodies
 Symptomatic Treatment

58. Type III hypersensitivity
 Involve reactions against soluble antigens
circulating in serum.
 Usually involve IgM, IgG antibodies.
 Antibody-Antigen immune complexes are deposited in
organs, activate complement, and cause inflammatory
damage.

59. PATHOGENESIS
i) Immune complexes are formed by interaction of soluble antibody and soluble
or insoluble antigen.
ii) Immune complexes which fail to get removed from body fluid get deposited
into tissues. Generally, small and intermediate sized antibodies and antigens
precipitate out of the body fluid and get deposited in tissues.
iii) Fc component of antibody links with complement and activates classical
pathway of complement resulting in formation of C3a, C5a and membrane
attack complex.
iv) C3a stimulates release of histamine from mast cells and its resultant effects of
increased vascular permeability and edema.
v) C5a releases proinflammatory mediators and chemotactic agents for
neutrophils.
vi) Accumulated neutrophils and macrophages in the tissue release cytokines
and result in tissue destruction.

60. Type III hypersensitivity – immune complex formation and
deposition
134
Immune complexes of
antigen (red dots) and
antibody form in
target organ
Immune complexes
activate complement
(green dots- C3a,and
C5a), and mast cells
(yellow cell) degranulate.
Inflammation and
edema occur, and
organ is damaged

61.  Generalized
 if immune complexes are formed in the circulation & are
deposited in many organ
 Localized to particular organs:
 kidney (glomerulonephritis), joints (arthritis),
 small blood vessels of the skin if the complexes are formed and
deposited locally (local Arthus reaction)

62. Arthus reaction
The Arthus reaction involves the in situ formation of
antigen/antibody complexes after the intradermal injection of an
antigen.
Occurs in previously sensitized (has circulating antibody), an
Arthus reaction occurs.
Arthus manifests as local vasculitis due to deposition of IgG-
based immune complexes in dermal blood vessels. Activation of
complement primarily results in cleavage of soluble complement
proteins forming C5a and C3a, which activate recruitment
of PMNs and local mast cell degranulation resulting in an
inflammatory response. Further aggregation of immune complex-
related processes induce a local fibrinoid necrosis with ischemia-
aggravating thrombosis in the tissue vessel walls.[3] The end
result is a localized area of redness and induration that typically
lasts a day or so

63. Serum sickness
 a condition that may develop when a patient is injected with a large amount of e.g.
antitoxin that was produced in an animal or other drugs
 After about 10 days, anti-antitoxin antibodies react with the antitoxin forming
immune complexes that deposit in tissues, walls of the blood vessels, skin,
joints, kidney
 Most common cause is penicillin and animal serum antitoxins

64. s/s
 Fever
 Arthralgia
 Rash
 Lymphadenopathy
 Malaise
 Polyarthritis and nephritis

65. Collaborative Management
 Usually Self limiting
 Symptomatic treatment
 Aspirin for pain
 Antihistimines for pruritus
 Steroids - prednisone

66. Type IV hypersensitivity
 the only type that is not antibody-mediated.
 contact hypersensitivity (poison ivy, reactions to
metals in jewelry);
 tuberculin-type hypersensitivity (the tuberculosis skin
test);
 granulomatous hypersensitivity (leprosy, tuberculosis,
schistosomiasis and Crohn’s disease).

67. Type IV. Cell-Mediated
 Initiated by specifically sensitized T lymphocytes which respond to an antigen by
producing and releasing certain lymphokines and they recruit, retain and activate
macrophages to destroy the antigen
 Antibodies and complement are not involved

68. PATHOGENESIS
i) The antigen is recognised by CD8+ T cells (cytotoxic T cells) and is processed
by antigen presenting cells.
ii) Antigen-presenting cells migrate to lymph node where antigen is presented to
helper T cells (CD4+ T cells).
iii) Helper T cells release cytokines that stimulate T cell proliferation and activate
macrophages.
iv) Activated T cells and macrophages release proinflammatory mediators and
cause cell destruction.

69. Type IV hypersensitivity – delayed-type or contact
156
Antigen is presented by APCs to antigen-specific memory T cells that
become activated and produce chemicals that cause inflammatory
cells to move into the area, leading to tissue injury. Inflammation by 2-
6 hours; peaks by 24-48 hours.
Antigen (red dots)
are processed by
local APCs
T cells (blue cells)
that recognize
antigen are
activated and
release cytokines
Inflammatory
response causes
tissue injury.

70.  In the TB skin test, a small amount of soluble antigen
(tuberculin) is injected into the skin.
 If individual is previously exposed to TB they’ll develop type
IV hypersensitivity.
 The T cells that are activated by the antigen secrete
cytokines that draw other cells to the site.
 Within four hours, neutrophils have arrived, followed by an
influx of monocytes and T cells at about 12 hours.
 The peak of activity is at about 48-72 hours, at which point
the area has become red and swollen.

71. 2. Transplant rejection
3. Contact dermatitis
4. Poison Ivy skin rashes
5. Local response to insect stings

73. Patch Testing
• Used to identify the allergen
• Skin contact with substances
to which the client is
potentially allergic
• Contact with a specific
allergen results in a delayed
reaction that develops in 48-
96 hours
• Substances applied under
occlusive tapes
• Localized erythema, blister,
swelling

74. MANAGEMENT
 Removal of the offending antigen
 Monitor reaction site and sites distal to the
reaction for circulation adequacy
 Antihistamines – minimal benefit
 Steroids

75. Type V. Stimulatory Reactions
• The IgG and IgM target a
hormone receptor.
• Example – Graves Disease
– An autoantibody binds to TSH
receptor sites in the thyroid
gland stimulating it to produce
thyroid hormones continually

76. Collaborative Management
 If one organ is involved like in Graves disease
,surgical removal or radiation can be done
 If more than one organ is involved then
immunosuppresion is warranted

77. THANK YOU