CN1: Allergic Conditions

Question 1

What type of the immune response releases vasoactive spasmogenic substances that act on vessel and smooth muscle and proinflammatory cytokines that recruit inflammatory cells?

Answer 1

Type I disease

Question 2

What can be classified on the basis of the immunologic mechanism that mediates the disease?

Answer 2

Hypersensitivity

Question 3

The humoral antibodies participate directly in injuring cells by predisposing then to phagocytosis or lysis in this type.

Answer 3

Type II dse

Question 4

What is the value of hypersensitivity?

Answer 4

It clarifies the manner in which the immune response ultimately causes injury or disease.

Question 5

What are best remembered as immune complex dses, in wc humoral Ab bind Ags and activate complement?

Answer 5

Type III dse

Question 6

In Type III disorders, the fractions of complement attract what?

Answer 6

Neutrophils

Question 7

What can produce tissue damage by the release of lysosomal enz and generation of toxic free radicals?

Answer 7

Neutrophils

Question 8

What is involved in tissue injury in wc cell-mediated immune responses w sensitized T lymphocytes are the cause of cellular and tissue injury?

Answer 8

Type IV disorders

Question 9

What is the prototype disorder for Type I: Anaphylactic type?

Answer 9

Anaphylaxis, bronchial asthma

Question 10

What is the immune mechanism for Type I: Anaphylactic Type?

Answer 10

Formation of IgE (cytotropic) Ab –> immediate release of vasoactive amines and other mediators from basophils and mast cells followed by recruitment of other inflammatory cells

Question 11

What is the prototype disorder for Type II: Cytotoxic type?

Answer 11

Autoimmune hemolytic anemia (AIHA)
Erythroblastosis fetalis
Goodpasture syndrome

Question 12

What is the immune mechanism for type II cytotoxic type?

Answer 12

Formation of IgG, IgM –> binds to Ag on target cell surface –> phagocytosis of target cell or lysis of target cell by C8,9 fraction of activated complement or Ab-dependent cellular cytotoxicity

Question 13

What is the prototype disorder for Type III immune complex type?

Answer 13

Arthus rxn
Serum sickness
SLE
Certain forms of acute glomerulonephritis

Question 14

What is the immune mechanism for type III Immune complex dse?

Answer 14

Ag-Ab complexes –> activated complement –> attracted neutrophils –> release of lysosomal enz and other toxic moieties

Question 15

What is the prototype disorder for Type IV Cell mediated (delayed) hypersensitivity type?

Answer 15

TB
Contact dermatitis
Transplant rejection

Question 16

What is the immune mechanism for type IV cell med hypersensitivity?

Answer 16

Sensitized T lymphocytes –> release of lymphokines and T cell mediated cytotoxicity

Question 17

What may be defined as rapidly developing immunologic rxn occuring within minutes after the combination of an Ag and Ab bound to mast cells or basophils in individuals previously sensitized to the Ag?

Answer 17

Anaphylactic type

can occur in local rxn or systemic disorders

Question 18

What usually follows an intravenous (IV) injection of an Ag to wc the host has already become sensitized?

Answer 18

Systemic rxn

often w/in minutes, a state of shock is produced and sometimes fatal.

Question 19

What depend on the portal of entry of the allergen and take the form of localized cutaneous swellings (skin allergy, hives), nasal and conjunctival discharge (allergic rhinitis and conjunctivitis), hay fever, bronchial asthma, or allergic gastroenteritis (food allergy)?

Answer 19

Local rxns

Question 20

Many local type I hypersensitivity rxns have 2 well-defined phases:

Answer 20

1. the initial response characterized by vasodilation, vascular leakage
2. depending on the location, smooth muscle spasm or glandular secretions

Question 21

The changes usually become evident within:

Answer 21

5-30 mins after allergen exposure

Subsides after 60 mins

Question 22

What are examples of second, late phase rxn?

Answer 22

Allergic rhinitis
Bronchial asthma

Question 23

When does second, late rxn set in?

Answer 23

2-8 hours later without additional exposure to Ag and lasts for several days.

Question 24

What is characterized by more intense infiltration of the tissues with eosinophils, neutrophils, basophils, monocytes, and CD4+ T cells as well as tissue destruction in the form of mucosal epithelial cell damage?

Answer 24

Late-phase rxn

Question 25

What are central to the development of type I hypersensitivity?

Answer 25

Mast cells and basophils

Question 26

What are bone marrow-derived cells that are widely distributed in the tissues?

Answer 26

Mast cells

Question 27

Difference of basophils and mast cells:

Answer 27

Basophils are not normally present in tissues

Question 28

Where are mast cells predominantly found?

Answer 28

Near the blood vessels
Nerves
Subepithelial sites

where local type I rxns tend to occur

Question 29

What contains membrane-bound granules that possess a variety of biologically active mediators?

Answer 29

Mast cell cytoplasm

Question 30

What does mast cells contain that bind basic dyes s/a toluidine blue?

Answer 30

Acid proteoglycans

stained granules often acquire a color that is different from that of the native dye, they’re referred to as metachromatic granules.

Question 31

What are activated by the cross-linking of high-affinity IgE Fc receptors?

Answer 31

Mast cells and basophils

Question 32

What other stimuli can trigger the mast cells?

Answer 32

C5a and C3a

anaphylatoxins

both act by binding to their receptors on the mast cell membrane

Question 33

Similarity of basophils and mast cells:

Answer 33

the presence of cell surface IgE Fc receptors as well as cytoplasmic granules

also:
- both circulate in the blood in extremely small numbers
- same to granulocytes, they can be recruited to inflammatory sites

Question 34

Other mast cell secretagogues include:

Answer 34

• macrophage-derived cytokines (e.g., IL-8)
• some drugs (codeine and morphine)
• melittin (present in bee venom)
• physical stimuli (e.g., heat, cold, sunlight)

Question 35

What is the differentiation of IgE-secreting B cells highly dependent on?

Answer 35

Induction of CD4+ helper T cells of Th2 type

Th2 type are pivotal in the pathogenesis of the type I hypersensitivity

type I rxns in humans = mediated by IgE

Question 36

What is the first step in the synthesis of IgE?

Answer 36

Presentation of the Ag (also called allergen) to precursors of TH2 by Ag-presenting dendritic cells.

Question 37

Th2 cells produce a cluster of cytokines which includes what?

Answer 37

IL-3, -4, -5, abd GM-CSF

Question 38

Because of its ability to recruit and activate inflammatory cells, it is considered important in the initiation of the late-phase response.

although its prodxn is also triggered by the activation of phospholipase A2, it isn’t a product of arachidonic acid metabolism

Answer 38

IL-4

Question 39

These polypeptides play a major role in the pathogenesis of type I hypersensitivity rxns bcs of their ability to recruit and activate inflammatory cells.

Answer 39

Cytokines

Question 40

What is an important mediator of the inflammatory response seen at the site of allergic inflammation?

Answer 40

TNF-a

Question 41

What is a potent cytokine that can attract neutrophils abd eosinophils, and favor their transmigration thru the vasculature and activate them in tissues?

Answer 41

TNF-a

Question 42

Inflammatory cells that accumulate at the sites of type I hypersensitivity rxns are additional sources of cytokines and histamine releasing factors that can cause what?

Answer 42

further mast cell degranulation

Question 43

A variety of chemotactic, vasoactive, and spasmogenic componds mediate Type I HPN rxns. Some, such as histamine and leukotrienes, are released rapidly from sensitized mast cells and are believed to be responsible for intense immediate rxns characterized by:

Answer 43

edema, mucus secretion, and smooth muscle spasm

many others, exemplefied by leukotrienes, PAF, TNF-a, and cytokines, set the stage for the late-phase response by recruiting additional leukocytes, basophils, neutrophils, and eosinophils.

Question 44

What can also produce soluble mediators, s/a IL-6, -8, and GM-CSF?

Answer 44

Epithelial cells

inflammatory cells also cause epithelial cell damage; epi cells aren’t passive bystanders, they also produce SM

Question 45

What can promote eosinophil chemotaxis?

Answer 45

Chemokines eotaxin and RANTES

impt in late-phse rxn = eo (favored by IL-5 & GM-CSF = from TH2 and mast cells)

Question 46

What are released from activated epithelial cells under the influence of mediators s/a TNF-a?

Answer 46

Chemokines eotaxin and RANTES

Question 47

What does eosinophils produce that are toxic to epithelial cells?

Answer 47

Major basic protein and eosinophil cationic protein

Question 48

What can produse leukotriene C4 and PAF and directly activate mast cells to release mediators?

Answer 48

Activated eosinophils and other leukocytes

Thus, the recruited cells amplify and sustain the inflammatory response without additional exposure to the triggering antigen.

Question 49

What is a major cause of symptoms in type I hpn dis, s/a allergic asthma?

Answer 49

Late-phase reaction

therefore, tx requires the use of broad-spectrum anti-inflammatory reagents s/a steroids

Question 50

TYPE I HYPERSENSITIVITY Summary

Answer 50

• complex dis resulting from an IgE-mediated triggering of mast cells and subsequent accumulation of inflammatory cells at sites of Ag disposition.
• events are regulated in large part by the induction of TH2-type helper T cells that promote synthesis of IgE and accumulation of inflammatory cells, particularly eosinophils
• clinical features result from release of mast cell mediators and accumulation of an eosinophil-rich inflammatory exudate

Question 51

What may occur after administration of heterologous proteins (e.g antisera), hormones, enz, polysaccharides, and drugs (s/a antibiotic penicillin)?

Answer 51

Systemic anaphylaxis

• the severity of the disorder varies with the level of sensitization
• the shock dose of Ag, however, may be exceedingly small, as, for example, the tiny amounts used in ordinary skin testing for various forms of allergies. Within minutes after exposure, itching, hives and skin erythema appear, followed shortly thereafter by a striking contraction of respiratory bronchioles and the appearance of respiratory distress.
• laryngeal edema results in hoarseness
• vomiting, abdominal cramps, diarrhea, and laryngeal obstruction follow, and patient may go into shock and even die within an hour
• effects of anaphylaxis must always be borne in mind when a therapeutic agent is administered
• although patients at risk can generally be identified by a previous hx of some form of allergy, the absence of such a hx does not preclude the possibility of an anphylactic reaction.

Question 52

• the severity of the disorder varies with the level of sensitization
• the shock dose of Ag, however, may be exceedingly small, as, for example, the tiny amounts used in ordinary skin testing for various forms of allergies. Within minutes after exposure, itching, hives and skin erythema appear, followed shortly thereafter by a striking contraction of respiratory bronchioles and the appearance of respiratory distress.
• laryngeal edema results in hoarseness
• vomiting, abdominal cramps, diarrhea, and laryngeal obstruction follow, and patient may go into shock and even die within an hour
• effects of anaphylaxis must always be borne in mind when a therapeutic agent is administered
• although patients at risk can generally be identified by a previous hx of some form of allergy, the absence of such a hx does not preclude the possibility of an anphylactic reaction.

Answer 52

Systemic anaphylaxis

Question 53

What reactions are exemplified by so-called atopic allergy?

atopy - implies a genetically determined predisposition to develop localized anaphylactic reactions to inhaled or ingested allergens

Answer 53

Local anaphylaxis

Question 54

What term implies a genetically determined predisposition to develop localized anaphylactic rxns to inhaled or ingested allergens?

Answer 54

Atopy

Question 55

About 10% of the population suffer from allergies involving localized anaphylactic rxns to:

• Extrinsic allergens (pollens, animal dander, house dust, fish, etc.)
• Urticaria
• Angioedema
• Allergic rhinitis (hay fever)
• some forms of asthma

What type of anaphylaxis rxn?

Answer 55

Local anaphylactic rxns

Question 56

(+) family hx of allergy is found in how many % of atopic individuals?

Answer 56

50% of atopic individuals

familial predisposition is NOT clear; but studies px w asthma reveal linkage to several loci, some map near the genes whose product regulate IgE response

candidate genes have been mapped to 5q31, where genes for cytokines IL-3, -4, -5, -9, IL-13, and GM-CSF are located

linkage has also been noted to 6p, close to the HLA complex

Question 57

Where is the genes for cytokines (IL-3,-4,-5,-9,-13, and GM-CSF) located?

Answer 57

5q31

Also 6p (close to HLA complex)

Question 58

What is higher in atopic individuals compared to the general population?

Answer 58

higher serum IgE

Question 59

In those genetically prone to develop allergies, environmental antigens referentially activate:

Answer 59

TH2 pathways

Question 60

What type is mediated by Ab directed towards Ag present on the surface of cells or other tissue components?

Answer 60

Type II hypersensitivity

The antigenic determinants may be instrinsic to the cell membrane, or they may take the form of an exogenous Ag, such as drug metabolite, absorbed on the cell surface. In either case, the hypersensitivity rxn results from the binding of Ab to normal or altered cell-surface Ag.

Has 3 Ab-dependent mechanisms

Question 61

● There are two mechanisms by which antibody and complement may mediate type II hypersensitivity: direct lysis and opsonization.

● In the first pattern, an antibody (IgM or IgG) reacts with an antigen present on the surface of the cell, causing activation of the complement system and resulting in the assembly of the membrane attack complex that disrupts membrane integrity by “drilling holes” through the lipid bilayer.

● In the second pattern, the cells become susceptible to phagocytosis by fixation of an antibody or C3b fragment to the cell surface (opsonization).

● This form of type II hypersensitivity most commonly involves blood cells – red blood cells, white blood cells, and platelets – but the antibodies can also be directed against extracellular tissue (e.g., glomerular basement membrane nephritis).
Clinically, such reactions occur in the following situations:
1. Transfusion Reactions
- in which cells from an incompatible donor react with autochthonous antibody of the host

2. Erythroblastosis Fetalis
   - in which there is an antigenic difference
   between the mother and the fetus, and
   antibodies (of the IgG class) from the mother cross the placenta and cause destruction of fetal red cells
3. Autoimmune Hemolytic Anemia
   - agranulocytosis, or thrombocytopenia in which individuals produce antibodies to their own blood cells, which are then destroyed
4. Pemphigus Vulgaris
   - in which antibodies against desmosomes interrupt intercellular junctions in epidermis, leading to formation of skin vesicles
5. Certain Drug Reactions
   - in which antibodies are produced that react with the drug which may be complexed to red cell antigen

Answer 61

Complement-Dependent Reactions

Question 62

● This form of antibody-mediated cell injury does not involve fixation of complement but instead requires the cooperation of leukocytes.

● The target cell, coated with low concentration of IgG antibody, are killed by a variety of non sensitized cells that
have Fc receptors. The latter bind to the target by their Fc receptors for the Fc fragment of IgG, and cell lysis proceeds without phagocytosis.

● ADCC may be mediated by monocytes, neutrophils, eosinophils, and NK cells. Although in most instances, IgG
antibodies are involved in ADCC, in certain cases (e.g., eosinophil- mediated cytotoxicity against parasites), IgE antibodies are used.

● ADCC may be relevant to the destruction of targets too large to be phagocytosed, such as parasites or tumor cells, and it may also play some role in graft rejection.

Answer 62

Antibody-Dependent Cell-Mediated Cytotoxicity

Question 63

● In some cases, antibodies directed against cell surface receptors impair or dysregulate function without causing
cell injury or inflammation.

● For example, in myasthenia gravis, antibodies reactive with acetylcholine receptors in the motor end plates of skeletal muscles impair neuromuscular transmission and therefore cause muscle weakness.

● The converse (i.e., antibody-mediated stimulation of cell function) is noted in Graves disease. In this disorder,
antibodies against the thyroid stimulating hormone receptor on thyroid epithelial cells stimulate the cells, resulting in hyperthyroidism

Answer 63

Antibody-Mediated Cellular Dysfunction

Question 64

What are the two mechanisms by wc Ab and complement may mediate type II hypersensitivity?

Answer 64

1) Direct lysis
2) Opsonization

Question 65

What happens in the first pattern of of complement dependent rxns?

Answer 65

Ab (IgM or G) reacts w Ag present on cell surface –> cause activation of complement system –> MAC (disrupts membrane integrity by drilling holes thru lipid bilayer)

Question 66

What happens in the second pattern of of complement dependent rxns?

Answer 66

The cells become susceptible to phagocytosis by fixation of Ab or C3b fragment to the cell surface (opsonization)

Question 67

What type involves blood cells and plts?

Answer 67

Type II hypersensitivity

Question 68

Hypersensitivity II rxns occur in:

Answer 68

1) transfusion rxns
2) erythroblastosis fetalis
3) AIHA
4) pemphigus vulgaris
5) certain drug rxns

Question 69

What is the condition in wc Ab against desmosomes interrupt intercellular junctions in the epidermis leading to formation of skin vesicles?

Answer 69

PV

Question 70

What requires the cooperation of the leukocytes and doesn’t involve fixation?

Answer 70

ADCC

Question 71

What are killed by a variety of nonsensitized cells that have Fc receptors?

Answer 71

Target cells coated w low conc of IgG Ab

Question 72

What involves Ab reactive w AchE receptors in the motor end plates of skeletal muscles impair neuromuscular transmission and therefore cause muscle weakness?

Answer 72

Myasthenia gravis

Question 73

In what condition does Ab against the thyroid stimulating hormone receptor on thyroid epithelial cells stimulate the cells resulting in hyperthyroidism?

Answer 73

Graves’ dse

Question 74

This reaction is induced by antigen
antibody complexes that produce tissue damage as a result of their capacity to activate the complement system.

● The toxic reaction is initiated when antigen combines with antibody, whether within the circulation (circulating immune complexes) or at extravascular sites where antigen may
have been deposited (in situ immune complexes).
○ Complexes produced in the circulation produce damage, particularly as they localize within blood vessel walls or when they are trapped in filtering
structures, such as the renal glomerulus.
○ The mere formation of antigen-antibody complexes in the circulation does not imply the presence of disease;
immune complexes are formed during many immune responses and represent a normal mechanism of antigen removal.

● The factors that determine whether the immune complexes formed in circulation will be pathogenic are not fully understood, but some possible influences are discussed here.

Answer 74

TYPE III HYPERSENSITIVITY (IMMUNE COMPLEX MEDIATED)

Question 75

What reaction is induced by Ag Ab complexes that produce tissue damage as a result of their capacity to activate the complement system?

Answer 75

Type III hypersensitivity (immune complex mediated)

Question 76

What are the 2 general types of Ag that cause immune complex-mediated injury?

Answer 76

(1) exogenous Ag (s/a foreign CHON, bact or virus
(2) under some circumstances, the individual can
produce antibodies against self components –
endogenous antigens.

The latter can be trace components present in the blood, or more commonly, antigenic components in cells and tissues. Immune-complex mediated diseases can be generalized, if immune complexes are formed in the circulation and are deposited in many organs, or localized to particular organs, such as the kidney (glomerulonephritis), joints (arthritis), or the small blood vessels of the skin if the complexes are formed and deposited locally (the local Arthus reaction). These two patterns are considered separately.

Question 77

What is the condition wherein small BV of skin of the complexes are formed and deposited locally?

Answer 77

Local Arthus rxn

Question 78

What is the prototype of a systemic immune complex disease?

Answer 78

Acute serum sickness

Question 79

What is a condition that at one time a frequent sequela to the administration of large amounts of foreign serum (e.g horse anti tetanus serum) used for passive immunization?

Answer 79

Acute serum sickness

It is now seen infrequently and in different clinical settings. For example, serum sickness may occur after administration of horse antithymocyte globulin for treatment of aplastic anemia or antibiotic therapy for microbial diseases.

Question 80

What can occur after administration of horse anti thymocyte globulin for AA tx or antibiotic therapy for microbial dses?

Answer 80

SS

Question 81

What can occur after administration of horse anti thymocyte globulin for AA tx or antibiotic therapy for microbial dses?

Answer 81

SS

Question 82

What is used in the prevention and treatment of acute rejection in organ transplantation and therapy of aplastic anemia?

Answer 82

Anti thymocyte globulin

Question 83

The pathogenesis of systemic immune complex disease
can be resolved into three phases:

Answer 83

1. Formation of antigen-antibody complexes in the circulation and
2. Deposition of the immune complexes in various tissues, thus initiating
3. An inflammatory reaction in dispersed sites throughout the body

The first phase is initiated by the introduction of antigen into the circulation and its interaction with immunocompetent cells, resulting in the formation of antibodies. Approximately
5 days after serum injection, antibodies directed against the serum components are produced, these react with the antigen still present in the circulation to form antigen-antibody complexes formed in the circulation are deposited in various tissues. The factors that determine whether immune complex formation will lead to tissue deposition and disease are not fully understood, but two possible influences are the size of the immune complexes and the functional status of the mononuclear phagocyte system:
○ Large complexes formed in great antibody excess are rapidly removed from the circulation by the mononuclear phagocyte system cells and are therefore relatively harmless. The most pathogenic complexes are of small or intermediate size (formed in slight antigen excess), circulate longer, and bind less avidly to phagocytic cells.
○ Because the mononuclear phagocyte system normally filters out the circulating immune complexes, its
overload or intrinsic dysfunction increases the probability of persistence of immune complexes in circulation and tissue deposition.

In addition, several other factors, such as charge of the immune complexes (anionic versus cationic), valency of the
antigen, avidity of the antibody, affinity of the antigen to various tissue components, three-dimensional (lattice) structure of the complexes, and hemodynamic factors, influence their tissue deposition.
○ In addition to the renal glomeruli, the favored sites of immune complex deposition are joints, skin, heart,
serosal surfaces, and small blood vessels.

● For complexes to leave the microcirculation and deposit within or outside the vessel wall, an increase in vascular permeability must occur. This is believed to occur when immune complexes bind to inflammatory cells through their Fc or C3b receptors and trigger release of vasoactive mediators as well as permeability-enhancing cytokines.
● Once complexes are deposited in the tissues, they initiate an acute inflammatory reaction (phase three). During this phase (approximately 10 days after antigen administration)
○ Activation of the complement cascade and
○ Activation of neutrophils and macrophages through their Fc receptors

Question 84

For complexes to leave the microcirculation and deposit within or outside the vessel wall, what must occur?

Answer 84

Increase vascular permeability

Question 85

Increased vascular permeability occurs when?

Answer 85

Immune complex bind to inflammatory cells through their Fc or C3b receptors and trigger vasoactive mediator release and permeability enhancing cytokines

Question 86

What are the complement activation proinflammatory effects?

Answer 86

1. Release of C3b, the opsonin that promotes
   phagocytosis of particles and organisms
2. Production of chemotactic factors, which direct the
   migration of polymorphonuclear leukocytes and
   monocytes (C5 fragments, C5b67)
3. Release of anaphylatoxins (C3a and C5a), which
   increase vascular permeability and cause
   contraction of smooth muscle
4. Formation of membrane attack complex (C5-9),
   causing cell membrane damage or even cytolysis

● Neutrophils and macrophages can be activated by immune complexes even in the absence of complement. These cells
have Fc receptors for IgG and therefore can bind to the Fc portion of the antigen-complexed IgG.
○ When several Fc receptor molecules are so occupied by aggregates of immune complexes, the inflammatory cells are activated.
● With either scenario, phagocytosis of antigen-antibody complexes by leukocytes drawn in by chemotactic factors results in the release or generation of a variety of additional
proinflammatory substances, including prostaglandins, vasodilator peptides, and chemotactic substances, as well
as several lysosomal enzymes including proteases capable of digesting basement membrane, collagen, elastin and
cartilage.
○ Tissue damage is also mediated by free oxygen radicals produced by activated neutrophils.
○ Immune complexes have several other effects. They cause aggregation of platelets and activate the Hageman factor; both of these reactions augment the inflammatory process and initiate the formation of microthrombi.
○ The resultant pathologic lesion is termed vasculitis if it occurs in blood vessels, glomerulonephritis if it occurs
in renal glomerulus, arthritis if it occurs in the joints, and so on.
● It is clear from the foregoing that complement-fixing antibodies (i.e., IgG and IgM) induce these lesions. Because IgA can activate complement by the alternative pathway, IgA-containing complexes may also induce tissue
injury.
○ The important role of complement in the pathogenesis of the tissue injury is supported by the observation that
experimental depletion of serum complement levels greatly reduces the severity of the lesions as does depletion of neutrophils.
○ During the active phase of the disease, consumption of complement decreases the serum levels.

Question 87

Morphology

Answer 87

● The morphologic consequences of immune complex injury are dominated by acute necrotizing vasculitis, with deposits of fibrinoid and intense neutrophilic exudation permeating
the entire arterial wall. Affected glomeruli are hypercellular because of swelling and proliferation of endothelial and mesangial cells, accompanied by neutrophilic and monocytic infiltration. The complexes can be seen on
immunofluorescence microscopy as granular lumpy deposits of immunoglobulin and complement and an electron microscopy as electron dense deposits along the glomerular basement membrane.
● If the disease results from single large exposure to antigen (e.g., acute poststreptococcal glomerulonephritis and acute serum sickness), all lesions tend to resolve, owing to catabolism of the immune complexes. A chronic form of serum sickness results from repeated or prolonged exposure to an antigen.
● Continuous antigenemia is necessary for the development of chronic immune complex disease because, as stated
earlier, complexes in antigen excess are the ones most likely to be deposited in vascular beds. This occurs in several human diseases, such as systemic lupus
erythematosus (SLE), which is associated with persistent exposure to autoantigens. Often, however, despite the fact that the morphologic changes and other findings suggest immune complex disease, the inciting antigens are unknown. Included in this category are rheumatoid arthritis, polyarteritis nodosa, membranous glomerulonephritis, and several other vasculitides.

Question 88

Local Arthus Reaction

Answer 88

● The Arthus reaction is defined as a localized area of tissue necrosis resulting from acute immune complex vasculitis usually elicited in the skin.

● The reaction can be produced experimentally by intracutaneous injection of antigen in an immune animal
having circulating antibodies against the antigen.
● Because of the excess antibodies, as the antigen diffuses into the vascular wall, large immune complexes are formed, which precipitate locally and trigger the inflammatory reaction already discussed.

● In contrast to IgE-mediated type I reactions, which appear immediately, the Arthus lesion develops over a few hours and reaches a peak 4 to 10 hours after injection, when it can be seen as an area of visible edema with severe
hemorrhage followed occasionally by ulceration. Immunofluorescent stains disclose complement, immunoglobulins, and fibrinogen precipitated within the
vessel walls, usually the venules.

● On light microscopy, these produce a smudgy eosinophilic deposit that obscures the underlying cellular detail, an appearance termed fibrinoid necrosis of the vessels. Rupture of these vessels may produce local hemorrhages,
but more often the vascular lumens undergo thrombosis, adding an element of local ischemic injury.

Question 89

What are the effects of immune complexes?

Answer 89

Cause aggregation of plts
Activate Hageman factor

• both augment inflammatory process and initiate formation of microthrombi

Question 90

What is the resultant pathologic lesion and occurs in BV?

Answer 90

Vasculitis

Question 91

Experimental depletion of serum complement lvls greatly reduces what?

Answer 91

the severity of lesions as does depletion of neutrophils

Question 92

What happens during the active phase of the dse?

Answer 92

Consumption of complement decreases the serum lvls

Question 93

What has deposits of fibrinoid and intense neutrophilic exudation permeating the entire arterial wall?

Answer 93

Acute necrotizing fasciitis

Question 94

What is necessary in development of chronic immune complex dse?

Answer 94

Continuous antigenemia

Question 95

What are the ones most likely be deposited in vascular beds?

Answer 95

Complexes in Ag excess

Question 96

What is associated w persistent exposure to autoAg?

Answer 96

SLE

Question 97

What is defined as a localized area of tissue necrosis resulting from acute immune complex vasculitis usually elicited in the skin?

Answer 97

Arthus rxn

Question 98

The Arthus lesion develops over a few hours and reaches a peak of how many hours after injection when it has visible edema with severe hemorrhage followed occasionally by ulceration?

Answer 98

4-10 hrs

Question 99

What can disclose complement, Ig, and fibrinogen pptated within the vessel walls, usually the venules?

Answer 99

Immunofluorescent stains

Question 100

What can disclose smudgy eosinophilic deposit that obscures the underlying cellular detail with an appearance termed fibrinoid necrosis of the vessels?

Answer 100

Light microscopy

Question 101

TYPE IV HYPERSENSITIVITY (CELL-MEDIATED)

Answer 101

● The cell-mediated type of hypersensitivity is initiated by
specifically sensitized T lymphocytes. It includes the classic delayed-type hypersensitivity reactions initiated by CD4+ T cells and direct cell cytotoxicity mediated by CD8+ T cells.

● It is the principal pattern of immunologic response not only
to a variety of intracellular microbiologic agents, particularly Mycobacterium tuberculosis, but also to many viruses,
fungi, protozoa, and parasites.

● So-called contact skin sensitivity to chemical agents and graft rejection are other instances of cell mediated reaction. Two forms of type IV hypersensitivity are described next:

Question 102

Delayed Type Hypersensitivity

Answer 102

● The classic example of delayed hypersensitivity is the tuberculin reaction, which is produced by the intracutaneous injection of tuberculin, a protein-lipopolysaccharide component of the tubercle bacillus. In a previously sensitized individual, reddening and induration of site appear in 8 to 12 hours, reach a peak in 24 to 72 hours, and thereafter slowly subside.

○ Morphologically, delayed-type hypersensitivity is characterized by the accumulation of mononuclear
cells around small veins and venules, producing a perivascular “cuffing”.
○ There is an associated increased microvascular permeability caused by mechanisms similar to those in other forms of inflammation.
○ Not unexpectedly, there is an escape of plasma proteins, giving rise to dermal edema and deposition of fibrin in the interstitium.
○ The latter appears to be the main cause of induration, which is characteristic of delayed hypersensitivity skin lesions.

● In fully developed lesions, the lymphocyte-cuffed venules show marked endothelial hypertrophy and, in some cases, hyperplasia. Immunoperoxides staining of the lesions reveals a preponderance of CD4 (helper) T lymphocytes.
● With certain persistent or non degradable antigens, such as tubercle bacilli, the initial perivascular lymphocytic infiltrate is replaced by macrophages over a period of 2 or 3 weeks.
○ The accumulated macrophages often undergo a morphologic transformation into epithelium-like cells and are then referred to as epithelioid cells.
○ A microscopic aggregation of epithelioid cells, usually surrounded by a collar of lymphocytes, is referred to as granuloma. This pattern of inflammation that is characteristic of type IV hypersensitivity is called granulomatous inflammation.
● The sequence of cellular events in delayed hypersensitivity can be exemplified by the tuberculin reaction, which begins with the first exposure of the individual to the tubercle bacilli.
○ Naive CD4+ T cells recognize peptides derived from tubercle bacilli in association with class II molecules on the surface of monocytes or epidermal dendritic (Langerhans) cells.
○ This initial encounter drives the differentiation of naive CD4+ T cells to Th1 cells. The induction of Th1 cells is
of signal importance because the expression of delayed hypersensitivity depends in large part on the cytokines secreted by Th1 cells.
○ Why certain antigens preferentially induce the Th1 response is not entirely clear, but the cytokine milieu subsequently.
○ Some of the sensitized Th1 cells so formed enter the circulation and remain in the memory pool of T cells for long periods, sometimes years.
○ On intracutaneous injection of tuberculin in an individual previously exposed to tubercle bacilli, the memory Th1 cells interact with the antigen on the
surface of antigen-presenting cells and are activated (i.e., they undergo blast transformation and proliferation).
○ These changes are accompanied by the secretion of the Th1 type cytokines, which are responsible for the expression of delayed-type hypersensitivity. Cytokines most relevant to this reaction and their actions are as
follows:
■ IL-2, a cytokine produced by macrophages, is critical for the induction of the Th1 response and hence delayed hypersensitivity. On initial encounter with a microbe, the resting macrophages attempt to phagocytose and kill the organism. The resting macrophages are not particularly adept at these functions. Nevertheless, this interaction leads to the production of IL-12, which, in turn, produces other cytokines, listed below. IL-12 is also a potent inducer of IFN-γ
secretion by T cells and NK cells. IFN-γ further augments the differentiation of Th1 cells.
■ IFN-γ has many effects and is an extremely important mediator of delayed-type hypersensitivity. It is a powerful activator of macrophages, causing further secretion of IL-12.
Activated macrophages are altered in several ways. Their ability to phagocytose and kill microorganisms is markedly augmented; they express more class II molecules on the surface,
thus facilitating further antigen presentation; their capacity to kill tumor cells is enhanced; and they secrete several polypeptide growth factors, such
as platelet-derived growth factor and TGF-β, that stimulate fibroblast proliferation and augment collagen synthesis. Thus activated, macrophages
serve to eliminate the offending antigen, and if the activation is sustained, fibrosis results.
■ IL-2 causes autocrine and paracrine proliferation of T cells, which accumulate at sites of delayed hypersensitivity; included in this infiltrate are some
antigen-specific CD4+ Th1 cells and many more bystander T cells activated by IL-2.
■ TNF-α and lymphotoxin are two cytokines that exert important effects on endothelial cells:
1. Increased secretion of prostacyclin,
which, in turn, favors increased blood
flow by causing local vasodilation;
2. Increased expression of E-selectin,
an adhesion molecule that promotes
attachment of the passing lymphocytes
and monocytes, and secretion of
low-molecular weight chemotactic
factors such as IL-8.
○ Together, all these changes in the endothelium facilitate the extravasation of lymphocytes and monocytes at the site of the delayed hypersensitivity reaction.
○ The process of which T cells and monocytes exit the vasculature is generally similar to that described for neutrophils. Involved is initial rolling
on the endothelium, followed by up-regulation of integrin and firm adhesion, and, ultimately, transmigration through the vessel wall.
● This type of hypersensitivity is a mechanism of defense against a variety of intracellular pathogens, including
mycobacteria, fungi, and certain parasites, and may also be involved in transplant rejection and tumor immunity. In addition to its beneficial, protective role, delayed-type hypersensitivity can also be a cause of
disease.
○ Contact dermatitis is a common example of tissue injury resulting from delayed hypersensitivity. It is evoked by coming in contact with urushiol, the
antigenic component of poison ivy or poison oak, and manifests in the form of a vesicular dermatitis.
○ The basic mechanism is similar to that described for tuberculin sensitivity. On reexposure to the plants, the sensitized CD4+ cells of the Th1 type first accumulate in the dermis, then migrate toward the antigen within the epidermis.
○ Here they release cytokines that damage keratinocytes, causing separation of these cells and formation of an intraepidermal vesicle. In this
form of delayed hypersensitivity reactions, especially those that follow viral infections, cytokine-producing CD8+ T cells may be the dominant effector cells

Question 103

T Cell-Mediated Cytotoxicity

Answer 103

● In this variant of type IV hypersensitivity, sensitized CD8+ T
cells kill antigen bearing target cells. Such effector cells are called cytotoxic T lymphocytes (CTLs).
○ CTLs directed against cell surface histocompatibility antigens play an important role in graft rejection.
○ They also play a role in resistance to virus infections.
In a virus-infected cell, viral peptides associate with the class I molecules within the cell, and the two are
transported to the cell surface in the form of a complex. It is this complex that is recognized by the TCR of cytotoxic CD8+ T lymphocytes.
○ The lysis of infected cells before viral replication is completed leads, in due course, to the elimination of the infection.
○ It is believed that many tumor-associated antigens may also be similarly presented on the cell surface.
CTLs therefore may also be involved in tumor immunity.
● Much has been learned about mechanisms by which CTLs kill their targets, and this knowledge may be of value in therapeutic modulation of T cell-mediated cytotoxicity in the settings of some autoimmune diseases.
○ Two principal mechanisms of T cell-mediated damage have been discovered:
(1) Perforin-granzyme-dependent killing and
(2) Fas-Fas ligand-dependent killing.
○ Perforins and granzymes are soluble mediators contained in the lysosome-like granules of CTLs. As its name indicates, perforin can perforate the plasma membranes of the target cells that are under attack by CD8+ lymphocytes.
○ At first, CD8+ T cells come in close contact with the target cells that are under attack by CD8+ lymphocytes.
○ This is followed by polymerization of the perforin molecules and their insertion into the target cell membranes, thus “drilling holes” into the membrane.
These pores allow water to enter the cells, thus causing osmotic lysis.
● The lymphocyte granules also contain a series of proteases called granzymes, which are delivered into the target cells
via the perforin-induced pores.
○ Once within the cell, granzymes activate apoptosis of the target cells by a different mechanism.
○ Activated CTLs express Fas-ligand, a molecule with homology to TNF-α, that can bind to Fas expressing target cells. This interaction leads to apoptosis.

Question 104

What mediates direct cell cytotoxicity?

Answer 104

CD8+ T cells

Question 105

What initiates classic delayed type hypersensitivity rxns?

Answer 105

CD4+ T cells

Question 106

What is a classic example of delayed hypersensitivity?

Answer 106

Tuberculin rxn

Question 107

What is a protein-lipopolysaccharide component of tubercle bacillus?

Answer 107

Tuberculin - intracutaneous injection

Question 108

In a sensitized individual, reddening and induration of the site appear in hour many hours?

Answer 108

8-12 hrs

Peak: 24-72 hrs then slowly subside

Question 109

What gives rise to dermal edema and fibrin deposition in the interstitium?

Answer 109

Escape of plasma proteins

Question 110

What reveals a preponderance of CD4 T lymphocytes?

Answer 110

Immunoperoxides staining of leison

Question 111

With certain persistent or nondegradable Ag, the initial perivascular lymphocytic infiltrate is replaced by what?

Answer 111

Macrophages over a pd of 2 or 3 wks

Question 112

Collar of lymphocytes

Answer 112

Granuloma

Question 113

What is a cytokine produced by macrophages and is critical for induction of Th1 response and hence delayed hypersensitivity?

Answer 113

IL-12

Question 114

What is a potent inducer of IFN-y secretion by T cells and NK cells?

Answer 114

IL-12

Question 115

What further augments the differentiation of Th1 cells?

Answer 115

IFN-y

Question 116

What has many effects and is an extremely important mediator of delayed-type hypersensitivity?

Answer 116

IFN-y

Question 117

What is a potent activator of macrophages and causing further secretion of IL-12?

Answer 117

IFN-y

Question 118

What is a potent activator of macrophages and causing further secretion of IL-12?

Answer 118

IFN-y

Question 119

What stimulates fibroblast proliferation and augment collagen synthesis?

Answer 119

Plt derived growth factor

TGF-B

Question 120

What causes autocrine and paracrine proliferation of T cells?

Answer 120

IL-2

Question 121

What are the effects of TNF-a and lymphotixin on endothelial cells?

Answer 121

(1) inc secretion of prostacyclin –> inc blood flow –> local vasodilation
(2) inc E-selectin

Question 122

What is an adhesion molecule that promotes attachment of passing lymphocytes and monocytes; and induction and secretion of LMW chemotactic factors (IL-8)?

Answer 122

E-selectin

Question 123

What are the two principal mechanisms of T cell mediated damage?

Answer 123

(1) perforin-granzyme-dependent killing

(2) Fas-fas ligand-dependent killing

Question 124

What are the steps in making an allergy diagnosis?

Answer 124

Step 1: DD
Step 2: etiologic agent
Step 3: detection of specific allergen

● For practical purposes, there are three types in making an allergy diagnosis.
○ Step 1: pertains to the differential diagnosis. All possible causes should be considered in an orderly manner.
○ Step 2: deals with how we arrive at an etiologic diagnosis, whether it is allergic or non allergic.
○ Step 3: is detection of the specific allergen/s involved.
● After confirming that the symptoms are truly allergic, a more specific diagnostic evaluation is in order to identify the antigen or antigens responsible for producing the symptoms.
● In addition, other variable factors should be assessed.
○ The degree of sensitivity to an antigen may vary in the same way that the degree of exposure to a clinically significant antigen varies.
○ Patients can be sensitive to multiple antigens and cumulative effects of exposure to several antigens may be important.
● Furthermore, the influence of non-immunologic factors on the symptoms has to be evaluated like the influence of
infection, inhaled irritants, fatigue, emotional factors and others. It is important to note whether these significantly influence the allergic problem.

○ Independently or cumulatively with other non-immunology factors or with the allergic or immunologic factors.
○ Or whether they vary widely in degree of significance. Because of these variables, one should consider carefully-taken history as the most important aspect of the clinical evaluation in pediatric allergy.

Question 125

Possible diagnosis that involves itching:

Answer 125

Urticaria-angioedema
Atopic dermatitis
Anaphylaxis

1. Itching
   ● Urticaria – angioedema
   ● Atopic dermatitis
   ● Anaphylaxis
2. Skin rash/eruptions
   ● Urticaria – angioedema
   ● Atopic dermatitis
   ● Anaphylaxis
   ● Cow’s milk allergy
3. Sneezing
   ● Allergic rhinitis
   ● Anaphylaxis
4. Rhinorrhea (runny nose)
   ● Allergic rhinitis
   ● Cow’s milk allergy
5. Diarrhea
   ● Anaphylaxis
   ● Food allergy
6. Vomiting
   ● Food allergy
7. Bloody stools
   ● Cow’s milk allergy

Question 126

Possible diagnosis that involves skin rash/eruptions:

Answer 126

Urticaria-angioedema
Atopic dermatitis
Anaphylaxis
Cow’s milk allergy

Question 127

Possible diagnosis that involves sneezing:

Answer 127

Allergic rhinitis

Anaphylaxis

Question 128

Possible diagnosis that involves rhinorrhea (runny nose):

Answer 128

Allergic rhinitis

Cow’s milk allergy

Question 129

Possible diagnosis that involves diarrhea:

Answer 129

Anaphylaxis

Food allergies

Question 130

Possible diagnosis that involves bloody stools:

Answer 130

Cow’s milk allergy

Question 131

Possible diagnosis that involves vomiting:

Answer 131

Food allergy

Question 132

Laboratory Exams

Answer 132

Non specific tests:
1. Smear of secretion for eosinophils
2. CBC and eosinophil count
3. Erythrocyte Sedimentation Rate (ESR)
4. Radiography
5. Stool examination
6. Urinalysis
7. Total IgE (PRIST)

Specific Tests:
Specific tests will identify the offending agent (specific IgE) causing the allergy symptoms. There may be no need to
proceed to the second set of tests if the first set, in correlation with the careful history, suggests that the problem is not allergic
1. Skin test
2. Radio allergo-sorbent test (RAST)
3. Provocative or challenge test
4. Patch Test

Routine Laboratory Tests
1. Blood count and ESR
● There are no abnormalities associated with the blood count and ESR in patients with allergic disease except for an eosinophilia of 3-7%.
● Higher eosinophil counts are seen in non- allergic asthma.
● Eosinophils in the respiratory tract secretions in patients with rhinorrhea or cough is a more useful diagnostic sign in allergy.
● A finding of greater than 5-10% eosinophils in nasal bronchial secretions is abnormal which is also true in the case of blood eosinophilia greater than 15% or 35% eosinophils/cmm.
● The presence of eosinophilia usually suggests that the patient’s symptoms will be sensitive to corticosteroid therapy, but it does not always suggest the presence of an allergy.
● The urine and stool of patients with unexplained urticaria will help rule out other non-allergic diseases.
Ascariasis may explain pronounced blood eosinophilia.
2. X-ray
● Chest X-ray may be necessary to rule out concomitant asthma as well as its complications. X-ray films of the paranasal sinuses are indicated occasionally in patients suspected to have sinusitis.
3. In Vitro tests

A. IgE measurement
1. PRIST: the paper radio-immunoabsorbent test is the most commonly used method in the measurement of total IgE. Asthma, allergic rhinitis and atopic dermatitis as seen in. Increased levels of IgE in typical forms of atopic dermatitis are of utmost importance in the differential diagnosis since they help support the diagnosis. Such findings likewise of IgE in typical
forms of atopic dermatitis are of utmost
importance in the differential diagnosis since they help support the diagnosis. Such findings likewise provide useful information regarding the likelihood of a child subsequently developing an
atopic disease.

2. RAST: just like any antibody, the finding of an elevated level of IgE will have to be reinforced by the information as to the specific antigens present in the IgE. This can be achieved by the radio- allergosorbent test (RAST). The correlation between RAST and provocation tests range from 75% to 100%. The RAST also correlates closely
   with the prick test as well as with clinical history.
   It is quite an expensive test so that most allergies would prefer to do skin testing first and use RAST in special situations like patients with widespread eczema, very young infants or in instances wherein the result of the skin test does not correlate with clinical history.

B. Histamine release test
● The histamine release test is a very sensitive test in allergy diagnosis and is reproducible. In this test, histamine is released and measured an hour
after the antigen is added to the basophils in the blood of a sensitive individual. This test is employed more in research laboratories than in clinical practice.
4. In Vivo tests
● The most commonly utilized technique for the demonstration of sensitivity of a patient to a number of offending agents is the skin test.
○ A small amount of the antigen is introduced into the skin either by prick or intradermal technique.
○ A wheal-flare reaction is seen if the patient is sensitive to the injected antigen. Type I or immediate type of hypersensitivity reaction is the basis for the phenomenon.

● Following the encounter of the specific antigen with cell- bound IgE antibody, there is release of vasoactive amines from the mast cells which are responsible for the erythema, and wheal-flare reaction
● This response is immediate (within minutes) and its timing and size of weal are of diagnostic importance. As a general rule, the faster the reaction and the larger the size of the weal, the more clinically relevant is the test antigen.

a. In vivo test: Skin test
● A late phase reaction at times is elicited and this occurs anywhere from 4 to 24 hours after the application of the test antigen. This latter response appears to be associated with the immediate IgE cutaneous responses and may also contribute to the late bronchial provocation response.
● False positive skin tests may occur with poorly prepared extracts containing non-specific irritants and after injection of excessive volume causing mechanical irritation.
● False negative reactions can be seen if the extract used is outdated or there is previous antihistaminic therapy, or in the very young and elderly.
● A positive skin test only demonstrates the presence of IgE antibody that is directed specifically against the test antigen. A positive test does not mean that the person has an allergic disease or that an allergic person has ever had a clinically significant reaction to the specific antigen.
● With inhalant antigens, correlation of positive skin test with history strongly suggests the presence of clinical sensitivity to the antigen.
● Conversely, a negative skin test and a negative history strongly suggest that the antigen is clinically insignificant. Particular attention must be used in
the interpretation of the skin tests for food, since they are much less reliable.

b. In vivo test: Provocation Challenge test
● Provocation challenge test is another method used to further document the sensitivity of a patient to an antigen. These procedures include conjunctival test in ophthalmic allergy, nasal and bronchial challenge in respiratory allergy as well as oral challenge in the case of ingestants.
● This test has been applied mostly in relation to asthma and allergic rhinitis.
● Bronchial provocation challenge tests can be performed by nebulisation of an aqueous antigen extract in the bronchial tree of the subject, and comparing its effects with that produced by an appropriate control solution.
● The effect on the pulmonary function is measured by the spirometer. The effect challenge is usually reflected in the fall of the forced expiratory volume
(FEV) and expressed in the concentration of antigen necessary to produce 20% fall in FEV1.

Question 133

Nonspecific tests:

Answer 133

Smear of secretion for eo
CBC and eo ct
ESR
Radiography
Stool exam
Urinalysis
Total IgE (PRIST)

Question 134

What will ID the offending agent (sp IgE) causing the allergy symptoms?

Answer 134

Specific tests

Question 135

Specific tests:

Answer 135

1) skin test
2) RAST (radio allergo-sorbent test)
3) provocative or challenge test
4) patch test

Question 136

Routine lab tests:

Answer 136

1) bld ct
2) ESR
3) x-ray
4) in vitro tests (IgE and histamine tests)
5) in vivo (skin test and provocation challenge test)

Question 137

OBJECTIVES IN THE TREATMENT OF COMMON
ALLERGIC DISORDERS

Answer 137

● The overall goal in the treatment of allergic disorders is to prevent the recurrence of the allergic state after it has been diagnosed. This can be accomplished by the following objectives:
1. To adequately identify the causative allergens.
2. To remove the offending allergen/s from the
patient’s environment.
3. To identify non-allergic triggers.
4. To avoid non-allergic triggers.
5. To use pharmacologic agents appropriately.
6. To institute allergy immunotherapy when total elimination of allergens is impossible.

● Allergic disease results from antigen antibody interaction that subsequently release mediators which are responsible
for the clinical symptoms.

● Therefore, the management of allergic disorders is based on an effort to adequately identify the causative allergens. Identifications of such allergens are usually achieved with
help of careful history taking and the judicious use of allergy skin testing.

● It must be remembered however, that elimination should not be based on the result of the skin test alone. It is only
when the history and the skin test correlate that the allergens in question are said to be contributing the symptoms.

● The vital role of a physician is to remove the offending food, or an offending contactant like cosmetics. In other instances, the total elimination is impossible like the removal of house dust mites, mold or pollen. In these cases, allergy immune-therapy is often considered.

● Instructions should be rigid and detailed for the preparation of an allergy-free environment with special attention to the child’s bedroom. The non-allergic triggers have likewise to
be identified and avoided.

● In many instances, the allergic state can be prevented by adequate avoidance of the environmental allergens and the use of appropriate pharmacologic agent

Question 138

Principles of Therapy in Allergic Disease

Answer 138

1. Avoidance of allergens or irritants
2. Pharmacologic therapy
3. Immunotherapy (hyposensitization or desensitization)
4. Prophylaxis

● Successful management of allergic disorders is based on avoidance of allergens or irritants, pharmacologic therapy, immunotherapy (hyposensitization or desensitization), and prophylaxis.

● Avoidance. When clinically relevant allergens are identified by history and judicious use of allergy skin tests, their
elimination or avoidance is all that is needed in many cases of IgE-mediated disease.
○ If the history and skin testing indicate reactivity to house dust mite or molds, or if dog or cat allergen is contributing to the patient’s symptoms, these allergens
should be eliminated from the home to the greatest extent possible.
○ The recommendation that a family pet be removed from a home is frequently difficult to implement. When
the allergic disorder is a serious one, such as asthma, and when the child has a positive skin test result to the dog or cat allergen, parents can generally be
persuaded to remove the animal.
○ When skin test results to dander are negative, the problem may be more difficult; most allergists believe that elimination of potentially sensitizing pets from the household of the allergic child is desirable prophylaxis.

● Allergy to house dust mites requires precautions to minimize exposure to mite allergens.
○ Avoidance in the bedroom is often sufficient because children spend more time there than in other rooms of the house.
○ Mattresses, box springs, and pillows should be encased in airtight, allergen-proof covers. Vacuuming the covered mattress at least weekly is necessary to
remove mites.
○ Beddings should be washed at least weekly in hot water (>70C); cool water does not kill the mites. There should be no carpet or rug in the bedroom because either may be a rich source of mites. A small cotton throw rug may be acceptable if it is washed at least weekly in hot water.
● There should be no upholstered furniture and no stuffed toys in the bedroom. When removal or carpet froma bedroom is impossible, treatmentof the carpet with a solution of ltannic acid inactivates mite allergens.
○ Repeated treatments of the carpetintervals of 2-3 months are necessary because the solution does not kill the mites. Benzyl benzoate (Acarosan) kills
mites; carpet treatment every few months is necessary to control mite population. Use tannic acid or benzyl benzoate is of less value than elimination of carpet.

● Household humidity should be kept at less than 50% to inhibit survival of mites. It is prudent to avoid use of vaporizers.
○ Dehumidifiers may be necessary in damp basements.
Air conditioning helps to control humidity and also reduces exposure to atmospheric pollens and molds.
○ If elimination of a cat from home is impossible, other measures that can reduce allergen exposure include
exclusion of the animal from the house, washing the cat more often than weekly, removal of carpets and upholstered furniture, and improvement of ventilation.
○ Cat allergen is ubiquitous in public places and homes without cats.

● Pharmacologic therapy is a major element in the management of diseases.
○ The drugs used have specific roles in the interruption of pathways leading to tissue damage as a consequence of antigen-antibody interaction.
○ Certain drugs, for example, modulate the antigen-induced release of mediators (histamine, leukotrienes) or block their actions; others affect the
tension of smooth muscle and still others prevent migration to the site of an allergic reaction of inflammatory cells having the potential for producing
tissue injury.
● Immunotherapy is appropriate for the treatment of allergic rhinitis or asthma mediated by IgE antibody-antigen
interactions caused by unavoidable inhalant allergens.
● A predisposition to form IgE antibodies to substances of
“high” allergenic potential is an important characteristic of the atopic state.
○ Therefore, prevention of exposure of infants and children at risk has a rational basis. It is appropriate to recommend breast-feeding for infants born into families with strong histories of hay fever, asthma or atopic dermatitis and to delay for at least 6 months the introduction of solid foods into the diet of such infants, especially foods of highly allergenic potentials such as eggs, cow milk, wheat, fish, citrus fruit, and peanut butter.
○ The nursing mother should avoid highly allergenic foods in her diet because there is evidence that the breast-fed infant can become sensitized to food antigens that are transmitted in breast milk. It is not definitively established whether postponing cow milk feedings in an atopic infant can prevent the development of cow milk allergy, of allergic diseases in general or of atopic dermatitis in particular, although there is some evidence of such effects
● Environmental exposure to high concentrations of house dust mite allergen is a risk factor for subsequent sensitization and asthma.
○ There are no prospective studies that indicate convincingly that avoidance of environmental exposure of atopic infants and children to other inhalant allergens such as dog and cat allergen lessens the likelihood of their sensitization, although such a result seems reasonable.

Question 139

● mild disease with little to no mucus lesions
○ membrane lesions
○ typically associated with infection
○ recurrent EM minor is usually associated with herpes simplex outbreaks.
○ other infection (viral, bacterial, protozoal, fungal or Mycoplasma pneumoniae) can also cause EM minor

Answer 139

Erythema Multiforme minor

Question 140

What is a reactive syndrome characterized by “target” vesiculobullous lesions of the skin and mucous membrane?

Answer 140

Erythema Multiforme

● Skin lesions may appear 3 to 14 days after insult (infection,
drug, etc.) and new lesions can continue to appear for up to
10 days.
● Mucous membrane involvement, if present, is painful and
debilitating. Fever, malaise, and weakness may also be
present.

Question 141

PE of EM

Answer 141

● Type: macules progressing to papules, vesicles and bullae
● Color: dull red rings alternating with cyanotic or violaceous rings
● Size: 1 to 2 cm
● Shape: target or iris lesions are typical
● Distribution: symmetric and bilateral, any parts of the body
● Sites of Predilection: palms, soles, dorsa of hands and feet, extensor surface of arms/legs, mucous membrane, oral, ocular and genital blistering and ulceration may be
present.
● Other organs: pulmonary and renal involvement may also occur

DIFFERENTIAL DIAGNOSIS

● Erythema Multiforme can be confused with viral exanthems, bullous diseases, urticaria, secondary syphilis, psoriasis or
pityriasis rosea

MICROSCOPIC CHARACTERISTICS
● Skin biopsy reveals dermal edema with a perivascular lymphocytic infiltrate and extravasated red blood cells. Necrotic keratinocytes lead to epidermal bullae formation

Question 142

● Rash appears 3 to 14 days after precipitating infection or drug.
● Mucous membrane involvement is mild if present at all. No systemic symptoms.
● Each episode resolves in 2 to 4 weeks, but recurrences can be frequent, especially in cases where herpes
simplex is the precipitation cause.

Answer 142

Erythema Multiforme minor

Question 143

What rash is extensive with bullous lesions and >2 mucous membranes are involved with systemic complication?

● (Steven-Johnson Syndrome) more severe disease with two mucous membranes affected and possible systemic symptoms such as fever and prostration.
● Typically associated with drugs (sulfonamides, phenytoin, barbiturates, phenylbutazone, penicillin, allopurinol)
○ Etiology is unknown in up to 50% cases. Other possible precipitants include vaccination, connective tissue disorders and rarely malignancy.
○ Pathogenesis is unclear, likely a cell-mediated cytotoxic reaction.

Answer 143

Erythema Multiforme major

● Rash appears and worsens until the precipitating cause is removed (i.e., discontinuation of drug).
● Rash is extensive with bullous lesions and >two mucous membranes are involved with systemic complication.
● Cheilitis stomatitis interferes with eating, vulvitis, and balanitis complicate micturition.
● Conjunctivitis and keratitis can lead to ocular impairment and lesions in the pharynx, larynx and trachea can occlude the airway.
● Fever and prostration are seen.

Question 144

In Erythema Multiforme major, what can interfere with eating, vulvitis, balanitis complicate micturition?

Answer 144

Cheilitis

Question 145

In Erythema Multiforme major, what can lead to ocular impairment and lesions in the pharynx, larynx, and trachea that can occlude the airway?

Answer 145

Conjunctivitis

Keratitis

Question 146

What can be seen in Erythema Multiforme major?

Answer 146

Fever and prostration

Question 147

What rash can resolve in 5-15 days?

Answer 147

Erythema Multiforme minor

Question 148

What is the most commonly used mtd in measurement of total IgE?

Answer 148

Paper radio-immunosorbent test (PRIST)

Question 149

Conditions that can be measured in PRIST:

Answer 149

Asthma
Allergic rhinitis
Atopic dermatitis

Question 150

What can measure the specific Ag present in IgE?

Answer 150

Radio-allergosorbent test (RAST)

Question 151

Conditions that can be measured in RAST:

Answer 151

Eczema

Question 152

In histamine release test, it is measured how many hours after the Ag is added to the basophils in bld of a sensitive individual?

Answer 152

1 hour

Question 153

In histamine release test, it is measured how many hours after the Ag is added to the basophils in bld of a sensitive individual?

Answer 153

1 hour

Question 154

What is the most commonly utilized technique for the determination of sensitivity of a px to a number of offending agents?

Answer 154

Skin test

Question 155

What reaction is seen if the px is sensitive to the injected Ag?

Answer 155

Wheal-flare rxn

Question 156

What is the basis for the phenomenon wheal-flare?

Answer 156

Type I or immediate type

Question 157

What is a reactive syndrome characterized by “target” vesicobullous lesions?

Answer 157

Erythema Multiforme

Question 158

Mild disease with little to no mucous membrane lesions:

Answer 158

Erythema Multiforme minor

Question 159

AKA Stevens-Johnson Syndrome

More severe dse w two mucous membranes affected and possible systemic symptoms s/a fever abd prostration:

Answer 159

Erythema Multiforme major

Question 160

What is most typically associated with infection?

Answer 160

Erythema Multiforme minor

Question 161

What is usually associated with herpes simplex outbreak?

Answer 161

Erythema Multiforme minor

Question 162

What is typically associated w drugs s/a Sulfonamides, phenytoin, barbiturates, phenylbutazone, penicillin, and allopurinol?

Answer 162

Erythema Multiforme major

Question 163

What are other possible precipitants in EM major?

Answer 163

Vaccination
CT disorders
Rarely malignancy

Question 164

What reaction occurs in EM major?

Answer 164

Cell-mediated cytotoxic rxn

Question 165

Skin lesions may appear after how many days after insult?

Answer 165

3-14 days

Question 166

New lesions can continue to appear for up to how many days?

Answer 166

10 days

Question 167

EM physical examination:

Answer 167

Type: Macules progressing to papules, vesicles, and bullae

Color: dull red rings alternating w cyanotic or violaceous rings

Size: 1-2cm

Shape: Target or iris lesions are typical

Distribution: Symmetric and bilateral, any parts of the body

Sites of predilection: palms, soles, dorsa of hands and feet, extensor surface of arms/legs

Mucous membrane: oral, ocular, genital blistering and ulceration may be present

Other organs: Pulmonary and renal involvement

Question 168

EM can be confused with:

Answer 168

• Viral exanthems
• Bullous dses
• Urticaria
• Secondary syphilis
• Psoriasis
• Pityriasis rosea

Question 169

EM microscopic characteristics:

Answer 169

Skin biopsy: dermal edema w a perivascular lymphocytic infiltrate and extravasated RBCs

Necrotic keratinocytes

Question 170

What can lead to epidermal bullae formation?

Answer 170

Necrotic keratinocytes

Question 171

What can inactivate mite allergens?

Answer 171

Solution of tannic acid

Question 172

Repeated tx of the carper are intervals of what?

Answer 172

2-3 months

Question 173

Repeated tx of the carper are intervals of what?

Answer 173

2-3 months

Question 174

What can kill mites?

Answer 174

Benzyl benzoate (Acarosan)

Question 175

Household humidity should be kept at less than what to inhibit mite survival?

Answer 175

Less than 50%

Question 176

What is a major element in dse mgmt?

Answer 176

Pharmacologic therapy

Question 177

What us an appropriate tx of allergic rhinitis or asthma mediated by IgE Ab-Ag interactions c/b unavoidable inhalant?

Answer 177

Immunotherapy

Question 178

What is an important characteristic of the atopic state?

Answer 178

Predisposition to form IgE Ab to substances of “high” allergenic potential

Question 179

What is a risk factor for subsequent sensitization and asthma?

Answer 179

Envi exposure to high conc of house dust mite allergens

Question 180

What is the general rule and clinically relevant in test antigen?

Answer 180

Faster rxn and larger wheal size

Question 181

In skin test, a late-phase rxn at times is elicited and occurs from how many hours after application of the test Ag?

Answer 181

4-24 hrs

Question 182

In skin test, a late-phase rxn at times is elicited and occurs from how many hours after application of the test Ag?

Answer 182

4-24 hrs

Question 183

What may occur w poorly prepared extracts containing non-specific irritants and after injection of excessive volume causing mechanical irritation?

Answer 183

False positive skin test

Question 184

What can be seen if the extract is outdated or or there is previous antihistamic therapy, or in very young and elderly?

Answer 184

False negative rxn

Question 185

What demonstrates the presence of IgE Ab that is directed specifically against the test Ag?

Answer 185

Positive skin test

Question 186

What mtd us used to further document the sensitivity of a px to an Ag?

Answer 186

Challenge test

Question 187

This test include conjunctival test in ophthalmic allergy, nasal and bronchial challenge in respi allergy and oral challenge in case of ingestants:

Answer 187

Challenge test

Question 188

What test has been applied mostly in relation to asthma and allergic rhinitis?

Answer 188

Challenge test

Question 189

What can be performed by nebulization of an aqueous Ag extract in the bronchial tree of subj, and comparing its effects w appropriate ctrl soln?

Answer 189

Bronchial provocation challenge tests

Question 190

What results from Ag-Ab interaction that subsequently releases mediators w/c are responsible for clinical symptoms?

Answer 190

Allergic dse

Question 191

Successful management of allergic disorders and the principles of therapy in allergic dse:

Answer 191

1. Avoidance of allergens or irritants
2. Pharmacologic therapy
3. Immunotherapy (hyposensitization or desensitization)
4. Prophylaxis

Question 192

What has types such as:

1. seasonal (pollens)
2. perennial (indoor inhalants)
   - house dust, feathers, animal danders, mold spores

Answer 192

Allergic Rhinitis

Question 193

➢ allergens deposited on nasal mucosa
➢ diffuse into epithelium
➢ initiate production of local IgE
➢ IgE-stimulated release of mast cell mediators
➢ subsequent recruitment of neutrophils, eosinophils, basophils and lymphocytes
➢ early and late phase reactions
➢ mucus production, edema, inflammation, pruritus and vasodilation

Answer 193

Allergic Rhinitis

Question 194

DIAGNOSIS & CLINICAL

MANIFESTATIONS of Allergic Rhinitis

Answer 194

1. sneezing
2. rhinorrhea – watery and profuse
3. nasal obstruction
4. itching of the nose, palate, pharynx and ears
5. itching, redness and tearing of the
   eyes
6. “rabbit nose” – wrinkling of nose to relieve itching and obstruction
7. “allergic salute” – rubbing of itchy nose

Question 195

DIFFERENTIAL

DIAGNOSIS of Allergic Rhinitis

Answer 195

1. Eosinophilic non-allergic rhinitis
2. Primary nasal mastocytosis
3. Neutrophilic (infectious rhinitis)
4. Vasomotor rhinitis

Question 196

TREATMENT of Allergic Rhinitis

Answer 196

1. Avoidance of allergens and irritants
2. Immunotherapy if unable to avoid allergens
3. Drug therapy
   – Antihistamines,
   decongestants, sympathomimetic
   – Nose drops sprays –
   short-term only to avoid
   rebound vasodilation and severe nasal obstruction
   – Cromolyn nasal solution (prophylaxis)
   – Topical corticosteroids (spray) – most effective
   – Leukotriene antagonists

Question 197

▪ wheals or welts of various sizes
▪ acute
▪ chronic – more than 6 weeks
▪ differ only in the depth of tissue
involvement
▪ foods and drugs are the common
causes

Answer 197

Urticaria angioedema (Hives)

Question 198

1. Antigen interacts with mast cell- or basophil- bound IgE
   ➢ release oh histamine
   ➢ vasodilation
   ➢ increased vascular permeability
   ➢ stimulates an axon reflex
   ➢ wheal and flare reaction
   Leukotrienes may contribute to the edema.
2. Complement system – C3a and C5a (anaphylatoxins)
3. Plasma kinin-forming system
   ➢ bradykinin – increased vascular
   permeability

Answer 198

Urticaria angioedema (Hives)

Question 199

DIAGNOSIS & CLINICAL

MANIFESTATIONS of Urticaria angioedema (Hives)

Answer 199

1. well-circumscribed sometimes coalescent, localized or generalized, erythematous, raised skin lesions
2. may be intensely pruritic or itch little
3. angioedema – edema of skin and
   submucosa or other tissues – upper respiratory and GIT
4. no laboratory tests establish the diagnosis

Question 200

TREATMENT of Urticaria angioedema (Hives)

Answer 200

1. Self-limited in most instances requiring little treatment other than antihistamines
2. Epinephrine – for active severe forms
3. Hydroxyzine – for cholinergic and chronic urticaria

Question 201

▪ erythema, edema, intense pruritus, exudation, crusting scaling
▪ inteepidermal vesiculation in acute stage
▪ genetically predetermined predilection

Answer 201

Atopic dermatitis

Question 202

1. def. of IgE isotype-specific “suppressor” T cell function - increased IgE
2. impairment of cell-mediated immunity
3. increased frequency of allergen - specific TH2 cells

Answer 202

Atopic dermatitis

Question 203

DIAGNOSIS & CLINICAL MANIFESTATIONS of Atopic dermatitis

Answer 203

1. erythematous, weepy patches in the cheeks then face, neck, wrists, hands, abdomen, and extensor aspect of extremities, later flexural areas.
2. marked pruritus
3. “mask of atopic dermatitis” – whitish hue and blanching of surrounding tissue
4. hyperpigmentation, scaling and lichenification
5. family history of asthma, hay fever of atopic dermatitis
6. increased IgE; eosinophilia
7. white dermatographism
8. atopic pleat or Dennie’s line or Morgan’s fold – accentuated lines/grooves below the margin of lower eyelids
9. sparsity of hair of the lateral portion of the eyebrows secondary to chronic rubbing

Question 204

DIFFERENTIAL DIAGNOSIS of Atopic dermatitis

Answer 204

1. seborrheic dermatitis
2. scabies
3. primary irritant dermatitis
4. allergic contact dermatitis
5. infectious eczematoid dermatitis
6. Wiskott-Aldrich syndrome

Question 205

TREATMENT of Atopic dermatitis

Answer 205

1. Avoidance of ingestant, injectant, contactant and atmospheric factors that can trigger itching
2. Extremes of temperature and humidity should be avoided
3. Garments – smooth-textured cotton. Wool should be avoided
4. Avoid soaps and detergents
5. Use bath oils, creams, or lotions
6. Local therapy wet dressings with Burrow’s solution
7. topical corticosteroid lotions or creams
8. antihistamines
9. antibiotics for secondary bacterial infection
10. topical steroid ointment after the acute phase subsides

Question 206

• Familial tendency

- Direct sensitiziation or via hapten-carrier mechanism

Answer 206

Food allergy

Question 207

DIAGNOSIS & CLINICAL MANIFESTATIONS of Food allergy

Answer 207

1. History
2. Allergy-like symptoms
3. Detection of high levels of histamine in the implicated food
4. Skin test

Clinical Manifestations:

1. GIT, vomiting, abdominal pain, diarrhea, bloody stools, protein-losing enteropathy, fat malabsorption
2. respiratory rhinorrhea, wheezing (rarely)
3. skin eczema, urticaria
4. CNS seizures, lethargy, headache, anxiety

Question 208

Tx for Food allergy

Answer 208

1. Avoidance – elimination of offending food from the diet
2. pharmacologic therapy – antihistamines, cromoglycate, self-administered epinephrine to prevent serious systemic reactions
3. immunotherapy hyposensitization has not been successful so far but further studies are needed

Question 209

▪ the prevalence of food allergy in infancy may be as high as 8%
▪ allergy to many foods may resolve within 1-2 yrs

Answer 209

Cow’s milk allergy

Question 210

➢ IgE-mediated in some cases

➢ No immunologic mechanism established

Answer 210

Cow’s milk allergy

Question 211

DIAGNOSIS & CLINICAL MANIFESTATIONS of Cow’s milk allergy

Answer 211

1. critical testing of foods by elimination and provocation method in a blind manner to eliminate emotional bias
2. skin testing with properly prepared food antigens
3. for cow’s milk allergy and anaphylactic food allergy, the history alone establishes the diagnosis

During the first year of life:

1. vomiting
2. watery, blood-streaked mucoid diarrhea
3. gastroesophageal reflux
4. enteropathy with loss of both protein and blood (in infants fed with whole pasteurized milk)
5. older infants – occult fecal blood loss, recurrent pulmonary infiltrates on x-ray, and multiple precipitating antibodies to cow milk proteins
6. enteropathies with varying combinations of malabsorption, steatorrhea, hypoalbuminemia, and fecal blood loss

Question 212

DIFFERENTIAL DIAGNOSIS of Cow’s milk allergy

Answer 212

1. food allergy – nuts, eggs, seafoods, milk
2. immune-mediated (e.g. celiac disease)
3. food additives – dyes, MSG, metabisulfite
4. food poisoning – botulinism, Clostridium perfringens, S. aureus
5. infections – Salmonella, E.coli, rotavirus, etc.
6. contaminants – heavy metals, antibiotics
7. pharmacologic agents – caffeine, tyramine, alcohol, histamine
8. GI disorders – GE reflux, pyloric stenosis, T-E fistula, etc.
9. enzyme deficiencies – galactosemia, PKU
10. malabsorption syndromes – lactose deficiency, cystic fibrosis
11. psychologic – school phobia
12. functional – irritable bowel syndrome, chronic non-spec. Diarrhea of infancy

Question 213

Tx for Cow’s milk allergy

Answer 213

1. treatment is directed at the clinical manifestations
2. offending food should be removed from the diet. The prescribed diet should be nutritionally adequate and will not impair the growth
3. most infants with IgE-mediated allergy to cow’s milk tolerate soy well but others are sensitive to it and may require the substitution of a protein hydrolysate
4. infants not able to tolerate hydrolysates are given amino acid-derived infant formulas

Question 214

▪ often an over diagnosed reaction especially in children
▪ usually occurs at least 7 days after administration of the drug unless there’s prior exposure
▪ occurs with low doses
▪ symptoms usually subside within 3 to 5 days after the drug is discontinued

Answer 214

Drug allergy

Question 215

Can be:

1. Type I hypersensitivity reaction
2. Type II (rare)
3. Type III
4. Type IV

Answer 215

Drug allergy

Question 216

DIAGNOSIS & CLINICAL MANIFESTATIONS of Drug allergy

Answer 216

1. accurate and detailed history needed for diagnosis
2. symptoms resemble hypersensitivity reactions such as anaphylaxis and serum sickness
3. diagnostic tests – skin test, RAST

Question 217

DIFFERENTIAL DIAGNOSIS of Drug allergy

Answer 217

Pseudo allergic drug reaction

Question 218

TREATMENT for Drug allergy

Answer 218

1. Withdrawal of offending agent
2. Pharmacologic
   ▪ Antihistamines – diphenhydramine
   1-2mg/kg/dose 3-4 times a day
   ▪ Sympathomimetics – epinephrine
   1:1000 – 0.01ml/kg subcutaneously
   ▪ Corticosteroids
   Prednisone
   1-2mg/kg/24 hrs in divided doses not to exceed 60mg orally

Question 219

▪ common skin disorder in childhood characterized by erythema, papules, vesicles, swelling and at times, weeping and itching
▪ it occurs 24 to 48 hours after exposure; may spread beyond the areas of contact and progresses for several days.
▪ Chronic cases are usually lichenified

Answer 219

Allergic contact dermatitis

Question 220

Involves type IV allergic reactions

Causes:

1. nickel in costume jewelry
2. perfume in soap
3. rubber in shoes
4. potassium bichromate (leather tanning agent)
5. plants – poison ivy
6. photosensitivity
7. mercury – rubber shoes, shoe toe caps, bathing caps
8. drugs – paraben preservatives
9. clothing – wool, wash and wear fabrics
10. animals – cats, dogs, horses, etc.

Answer 220

Allergic contact dermatitis

Question 221

Diagnosis tests on Allergic contact dermatitis:

Answer 221

– extensive history
– careful physical examination
– exclusion of diseases characterized by eczematous lesions

Question 222

In Allergic contact dermatitis, manifestations depend on the cause:

Answer 222

1. feet lesions are symmetrically sparing the interdigital spaces
2. blisters in lines and streaks
3. earlobe, neck, wrist dermatitis
4. axillary dermatitis
5. dermatitis on other parts of the body where there is contact with the allergen

Question 223

DIFFERENTIAL DIAGNOSIS of Allergic contact dermatitis

Answer 223

1. Eosinophilic non-allergic rhinitis
2. Primary nasal mastocytosis
3. Neutrophilic (infectious rhinitis)
4. Vasomotor rhinitis

Question 224

Tx for Allergic contact dermatitis

Answer 224

1. Antihistamines e.g., diphenhydramine and hydroxyzine
2. Warm water compresses to remove medications applied at home
3. Avoid substances that might further irritate or sensitize the damaged skin
4. To relieve inflammation in the acute phase: Cool H2O compresses kept moist and in place for at least 45 minutes 3x daily
5. Corticosteroid creams
6. For disseminated skin lesions: short-course systemic corticosteroid, 2mg/kg per day in divided doses
7. For infectious, suspected, or present-topical erythromycin

Question 225

Site for ID test

Answer 225

Forearm 4 finger-width below AC

Question 226

ID testing amount:

Answer 226

< or = 0.5mL

Question 227

Gauge of needle used in ID testing

Answer 227

25-27 deg

Question 229

Inches ID test:

Answer 229

1/2 to 5/8

Question 230

ID test angle:

Answer 230

5-15 deg

Question 231

What syringe is used in ID testing?

Answer 231

Tuberculin syringe

Question 232

Management EM minor and Major

Answer 232

Erythema Multiforme minor
● Rash self-resolves in 5 to 15 days.
● Symptomatic relief can be obtained with the following:
a. Bath with colloidal oatmeal
b. Emollients
c. Topical steroids are effective if used in appropriate strength
d. Antihistamines may be somewhat helpful in controlling itchiness
e. Severe cases may require systemic steroids
f. Control of herpes outbreaks in recurrent cases of EM minor with prophylactic acyclovir is indicated

Erythema Multiforme major
● Identification and elimination of the precipitating agent is critical.
● Supportive care includes:
a. Wound care, including baths with gentle cleaners
b. Topical steroids in appropriate strength (15% hydrocortisone, 25% hydrocortisone)
c. Widespread denudation of the skin requires hospitalizations and thermoregulation and food administration (especially in cases with extensive oral involvement). Systemic steroids are of questionable efficacy. Constant culture and local debridement should be done to prevent infection and risk of sepsis until skin fully heals