ALLERGY and

ANAPHYLAXIS
 ALLERGY
ALLERGY:
First coined in 1906 by von Pirquet

Used to refer to patients who expressed an altered state of

reactivity to common environmental antigens

With the discovery in the 1960s that most patients produce IgE
antibodies to antigens that trigger their illness, it is often used
interchangeably with IgE-MEDIATED ALLERGIC DISEASE

ATOPY:
Derived from the Greek atopos, meaning out of place
Used to describe patients with IgE-mediated diseases
 ALLERGY
ATOPIC ALLERGY:
Implies a familial tendency to manifest one or more of
the following conditions:
Asthma
Rhinitis
Urticaria
Eczematous dermatitis (atopic dermatitis)

SENSITIZATION:
The fixation of IgE to human mast cells and basophils
A process which prepares the mast cells and
basophils for subsequent antigen-specific activation
 Features of Allergic Diseases:
ALLERGEN:
Refers to an antigen that triggers an IgE response in genetically
predisposed individuals
Major allergens:
House-dust mite (Dermatophagoides pteronyssinus)
Cat dander
Tree, grass and weed pollens

TYPE 2 HELPER (TH2) T CELLS:

Nonatopic individuals:
Respond to allergens with proliferation of T helper 1 (Th1) cells
Secrete cytokines (IFN-) which are involved in the elicitation of allergen-specific IgG
antibodies
Generally involved in the eradication of intracellular organisms (e.g.,
mycobacteria)
Activate phagocytes and promote the production of opsonizing and complement-fixing
antibodies
 Features of Allergic Diseases:
TYPE 2 HELPER T CELLS:
Atopic individuals:
Respond to allergens with a brisk expansion of T helper type 2 (Th2) cells
Secrete cytokines favoring IgE synthesis
Involved in host defense against extracellular organisms (e.g.,
parasites)

Th2 CYTOKINES:
IL-4 and IL-9:
play a key role in immunoglobulin isotype switching to IgE
IL-5 and IL-9:
further enhance IgE synthesis and play a role in the differentiation and
development of eosinophils
IL-3, IL-4 and IL-9:
contribute to mast cell development
T Cell Differentiation:
Role of TH2 Cytokines in Allergy:
 IgE and its RECEPTORS:
1. FcRI:
The high-affinity Fc receptor for IgE
Composed of:
1) one chain- responsible for IgE binding
2) one chain
3) 2 disulfide-linked chains
The and chains provide for signal transduction that follows the aggregation of the sensitized
tetrameric receptors by polymeric antigen
Aggregation of FcRI initiates pathways for generation of bioactive products:
1) lipid mediators
2) cytokines

2. FcRII- low-affinity Fc receptor

The acute allergic response is dependent on IgE and its ability to

bind selectively to the chain of the high-affinity FcRI or the low-
affinity FcRII
 EOSINOPHILS:
Allergic diseases are characterized by peripheral blood and tissue eosinophilia

Eosinophils contain dense intracellular granules that contain inflammatory proteins:

Major basic protein (MBP)
Eosinophil-derived neurotoxin
Peroxidase
Cationic protein

Eosinophil granule proteins have the following effects:

damage of epithelial cells
induce airway hyperresponsiveness
cause degranulation of basophils and mast cells

Eosinophils are a rich source of leukotrienes (cysteinyl leukotriene C4) which has the
following effects:
airway smooth muscle contraction
increased vascular permeability

Other secretory products causing allergic tissue inflammation include:

Cytokines (IL-4, IL-5, TNF-)
Proteolytic enzymes
Reactive oxygen intermediates
 Antigen-Presenting Cells (APCs):
ANTIGEN-PRESENTING CELLS (APCs):
Include dendritic cells, Langerhans cells, monocytes and macrophages
Play an important role in the induction of allergic inflammation by:
presenting allergens to T cells
contributing to the local recruitment of effector cells

1. DENDRITIC CELLS:
Together with Langerhans cells prime nave T cells and are responsible for
the primary immune response (sensitization phase of allergy)
Immature dendritic cells reside in peripheral sites (skin, intestinal lamina
propia, lungs)
Take up antigens in tissues and then migrate to the T cell areas in locally
draining lymph nodes
In the lymph nodes, they directly present processed antigens to resting T
cells to induce their proliferation and differentiation
 Antigen-Presenting Cells (APCs):
2. LANGERHANS CELLS:
The formation of (FcRI) / IgE / allergen complexes on the
APC cell surface markedly facilitates allergen uptake and
allergen presentation
FcRI-positive Langerhans cells bearing IgE molecules is a
prerequisite for provocation of eczematous lesions by
aeroallergens applied to the skin of patients with atopic
dermatitis

3. MONOCYTE-MACROPHAGES:
FcRII in association with monocytes and macrophages can
facilitate antigen capture
Cross-linking of FcRI and FcRII on monocytes-macrophages
can lead to release of inflammatory mediators
 MAST CELLS:
Mature mast cells do not usually circulate in the blood

Widely distributed throughout connective tissues where

they often lie adjacent to blood vessels and beneath
epithelial surfaces that are exposed to the external
environment (respiratory tract, GIT, skin)

2 subpopulations:
1) mast cells with tryptase:
Predominant type found in the lung and small intestinal mucosa
2) mast cells with both tryptase and chymase:
Predominant type found in the skin, GI mucosa and blood vessels
 MAST CELLS:
Contain or produce mediators that have different effects on
allergic inflammation and organ function:
1) Pre-formed granule-associated mediators:
Histamine
Serine proteases
Proteoglycans
2) De novo synthesized membrane-derived lipid metabolites of
arachidonic acids:
Prostaglandin D2 (PGD2): the major cyclo-oxygenase product of mast cells
Leukotrienes (LTC4, LTD4, LTE4): the major lipoxygenase products of mast cells
3) Cytokines
IL-4, IL-13, GM-CSF: promote Th2-type responses
TNF-, IL-6: promote inflammation
TGF, VECGF: regulate tissue remodeling
4) Chemokines
The Mast Cell:
Arachidonic Acid Metabolites:
 Mechanisms of Allergic Tissue
Inflammation:
1. EARLY PHASE RESPONSE:
The immediate response after introduction of allergen into target organs
Results from mast cell degranulation accompanied by the release of

preformed mediators
Occur within 10 mins after allergen exposure and resolving within

1-3 hrs
Acute reactions are associated with local vascular permeability leading

to:
Leakage of plasma proteins
Tissue swelling
Increased blood flow
Manifested depending on the target organ in which the allergen
challenge takes place:
Itching (skin)
Sneezing (nose)
Wheezing (lung)
Acute abdominal cramps (GIT)
 Mechanisms of Allergic Tissue
Inflammation:
2. LATE PHASE RESPONSE (LPR):
Occur within hours of allergen exposure, reaching a maximum

of 6-12 hrs and resolving by 24 hrs

Clinical manifestations:
1) skin- edema, redness, induration
2) nose- sustained nasal blockage
3) lung- wheezing
Associated with the early infiltration of neutrophils followed by
basophils, monocytes and macrophages, and Th2-type cells
Recruitment of inflammatory cells from the circulation:
Several hours after allergen exposure, TNF-, which is released by
activated mast cells, induces the endothelial expression of the following
leading to transendothelial migration of inflammatory cells:
E-selectin
Intercellular cell adhesion molecules (ICAM-1)
Vascular cell adhesion molecules (V-CAM)
 Mechanisms of Allergic Tissue
Inflammation:
2. LATE PHASE REACTION (LPR):
Preferential accumulation of eosinophils mediated by the following adhesion

molecules:
41 integrin or VLA-4
VCAM-1
IL-4
IL-13

Chemokines (chemotactic cytokines) that play a role in the directed migration

of inflammatory cell:
1) Eotaxins- chemoattractants for eosinophils
2) Chemoattractants for both eosinophils and mononuclear cells:
RANTES
Macrophage inflammatory protein 1
Monocyte chemotactic protein (MCP)-3
Monocyte chemotactic protein (MCP)-4

The above chemoattractants have been detected in epithelium, macrophages,

lymphocytes and eosinophils at sites of LPR and allergic tissue inflammation
 Mechanisms of Allergic Tissue
Inflammation:
3. CHRONIC ALLERGIC DISEASE:
Tissue inflammation can persist for days to years
Factors that contribute to persistent tissue inflammation:
1. Recurrent exposure to allergens and microbial agents
2. Repeated stimulation of allergic effector cells:
Mast cells
Basophils
Eosinophils
Th2 cells cytokines (IL-3, IL-5, GM-CSF) secreted during allergic reactions can prolong survival
of allergic effector cells due to delayed apoptosis
3. Self-generation of eosinophils (induced by IL-5) contributes to continued
damage of local tissue
4. Tissue remodeling leading to irreversible changes in target organs (induced by
Th2 cytokines):
IL-4, IL-9, IL-13: mucus hypersecretion and mucus cell metaplasia
IL-4, IL-13: fibroblast growth and extracellular matrix prorein synthesis
IL-5, IL-9, IL-11, TGF-: subepithelial fibrosis
IL-11: subepithelial fibrosis, enhanced collagen deposition, myofibroblast and fibroblast
accumulation
 ANAPHYLAXIS

A life-threatening response of a
sensitized human to a specific
antigen

Hallmark:
onset appears within seconds or minutes
after introduction or administration of a
specific antigen
 PREDISPOSING FACTORS:
HORMONES: insulin, vasopressin, parathormone

ENZYMES: trypsin, chymotrypsin, penicillinase, streptokinase

POLLEN EXTRACTS: ragweed, grass, trees

NONPOLLEN EXTRACTS: dust mites, dander of cats, dogs, horses and laboratory
animals

FOOD: milk, eggs, seafood, nuts, grains, beans, gelatin in capsules

ANTISERUM: antilymphocyte gamma globulin

OCCUPATION-RELATED PROTEINS: latex rubber products

HYMENOPTERA VENOM: yellow jacket, yellow and baldfaced hornets, paper wasp,
honey bee, imported fire ants
 PREDISPOSING FACTORS:
Polysaccharides- dextran, thiomerosal (vaccine
preservative)

Drugs:
Protamine
Antibiotics- penicillins, cephalosporins, amphotericin B,
nitrofurantoin, quinolones
Local anesthetics- procaine, lidocaine
Muscle relaxants- suxamethonium, gallamine, pancuronium
Vitamins- thiamine, folic acid
Diagnostic agents- sodium dehydrocholate,
sulfobromophthalein
Occupation-related chemicals- ethylene oxide
 MANIFESTATIONS:
Upper or lower airway obstruction or both, resulting in
respiratory distress
Laryngeal edema- experienced as a lump in the throat, hoarseness
or stridor
Bronchial obstruction and brochospasm- associated with a feeling
of tightness in the chest and/or audible wheezing

Cutaneous manifestations:
URTICARIAL ERUPTIONS
WHEALS- eruption of intensely pruritic well-circumscribed, discrete lesions with
erythematous, raised, serpiginous borders and blanched centers which may be
localized or disseminated
HIVES- composed of wheals which coalesce
ANGIOEDEMA- a localized, nonpitting, deeper edematous cutaneous
process which may be asymptomatic or cause a burning or stinging
sensation
 MANIFESTATIONS:
Gastrointestinal manifestations:
Nausea
Vomiting
Crampy abdominal pain
Diarrhea

Vascular collapse

Shock

Sometimes symptoms occur without antecedent

respiratory difficulty
 PATHOPHYSIOLOGY:
BRONCHIAL OBSTRUCTION:
Marked hyperinflation of the lungs on gross and microscopic examination
Microscopic findings:
Luminal secretions, peribronchial congestion, submucosal edema, eosinophilic
infiltration
Cysteinyl leukotrienes- alter pulmonary mechanics by causing
marked bronchiolar constriction

ANGIOEDEMA:
Attributed to the release of endogenous histamine
Results in death by mechanical obstruction
Evident in the epiglottis and larynx, also in the hypopharynx and trachea
Microscopic findings:
Wide separation of the collagen fibers and the glandular elements
Vascular congestion
Eosinophilic infiltration
 PATHOPHYSIOLOGY:
VASCULAR COLLAPSE:
Death without antecedent hypoxia from respiratory
insufficiency is due to presumptive loss of intravascular
volume secondary to visceral congestion
PGD2 metabolites in addition to histamine play a role
in the hypotensive anaphylactic reactions

ECG ABNORMALITIES:
Reflect a primary cardiac event or be secondary to a
critical reduction in blood volume
The cysteinyl leukotrienes may be involved in the
pathobiologic process in patients with myocardial
ischemia with or without infarction
 DIAGNOSIS:
ANAPHYLAXIS is highly likely when any 1 of the ff 3 criteria is fulfilled:

1. Acute onset of illness of mins to several hrs duration involving the skin,
mucosal tissue or both (e.g., pruritus, flushing, generalized hives, edema
of lips, tongue and uvula) PLUS at least 1 of the ff:
Respiratory compromise (e.g., dyspnea, stridor, wheezing, hypoxia)
Cardiovascular compromise (e.g., hypotension, vascular collapse)

2. >2 of the ff that occur rapidly after exposure to a likely allergen of mins
to several hrs duration
Skin or mucosal tissue involvement
Respiratory compromise
Cardiovascular compromise
GI symptoms that are persistent (e.g., crampy abdominal pain, vomiting)

3. Decreased BP after exposure to known allergen of mins to several hrs

duration:
SBP < 90 mm Hg or >30% decrease from that persons baseline
 DIAGNOSIS:
Depends on an accurate history revealing the onset
of the appropriate symptoms and signs within
minutes after the responsible material is
encountered

Radioimmunoassays demonstrate specific IgE

antibodies in patients with anaphylactic reactions

Elevation of -tryptase levels in serum implicate

mast cell activation in an adverse systemic reaction
(venom-related, drug-related, idiopathic)
 TREATMENT:
Epinephrine:
Provides both - and -adrenergic effects, resulting in:
vasoconstriction
bronchial smooth muscle relaxation
attenuation of enhanced venular permeability

Mild symptoms (pruritus, urticaria) - 0.3-0.5 mL of 1:1000 epinephrine SC or

IM repeated as required at 20-min intervals

IV infusion- 2.5mL diluted 1:10,000 at 5- to 10-min intervals

Volume expanders (i.e.,saline)- to replace intravascular

volume due to postcapillary venular leakage

Vasopressor agents (e.g.,dopamine)- for intractable

hypotension
 TREATMENT:
Oxygen via a nasal catheter

Intermittent positive-pressure breathing of

oxygen with inhaled or nebulized albuterol

Endotracheal intubation or tracheostomy

Ancillary agents:
Antihistamines
Diphenhydramine- 50 to 100mg IM or IV- urticaria-angioedema
Aminophylline at 0.25 to 0.5g IV- bronchospasm
Glucocorticoids- not effective for the acute event but
may alleviate later recurrence of bronchospasm,
hypotension or urticaria
 URTICARIA and ANGIOEDEMA:
URTICARIA:
Involves only the superficial portion of the dermis
Presents as well-circumscribed wheals with erythematous raised serpiginous
borders and blanched centers
May coalesce to become giant wheals

ANGIOEDEMA:
A well-demarcated localized edema involving the deeper layers of the skin,
including the dermis and subcutaneous tissue

Recurrent episodes of urticaria and/or angioedema of less than 6

weeks duration are considered ACUTE, whereas attacks persisting
beyond this period are designated CHRONIC

Incidence:
May occur in any age group, increasing in frequency after adolescence, with the
highest incidence in the 3rd decade of life
 CLASSIFICATION of URTICARIA /
ANGIOEDEMA:
1. IgE-dependent

A. Specific antigen sensitivity

Pollens, food, drugs, fungi, molds, Hymenoptera venom, helminths

B. Physical
Dermographism- apperance of a linear wheal at the site of a brisk stroke with a
firm object or by any configuration appropriate to the eliciting event
Cold- located at body areas exposed to low ambient temperature or cold objects
Solar- urticaria resulting from a response to specific portions of the light
spectrum
Cholinergic- pruritic wheals of small size (1-2 mm) surrounded by a large area of
erythema attributed to a rise in core body temperature
Vibratory- idiopathic or occur after years of occupational exposure
Exercise-related

C. Autoimmune
 CLASSIFICATION of URTICARIA /
ANGIOEDEMA:
2. Bradykinin-mediated
A. Hereditary angioedema: C1 inhibitor deficiency: null (type 1) and
dysfunctional (type 2)
B. Acquired angioedema: C1 inhibitor deficiency: anti-idiotype and anti-C1
inhibitor
C. Angiotensin-converting enzyme enhibitors (ACEI)

3. Complement-mediated
A. Necrotizing vasculitis
B. Serum sickness
C. Reactions to blood products

4. Nonimmunologic
A. Direct mast cell-releasing agents (opiates, antibiotics, curare, D-tubocurarine,
radiocontrast media)
B. Agents that alter arachidonic acid metabolism (ASA, NSAIDs, azo dyes, benzoates)

5. Idiopathic
 MANIFESTATIONS:
Urticarial eruptions are distinctly pruritic

May involve any area of the body from the scalp to the soles of the
feet

Appear in crops of 24- to 72-hour duration

Old lesions fade as new ones appear

Most common sites for urticaria- face and extremities

Most common sites for angioedema- periorbital and in the lips

Self-limited in duration

No discoloration occurs unless there is an underlying process

leading to superimposed extravasation of erythrocytes
 PATHOPHYSIOLOGY:
The pathology of urticaria and angioedema is characterized by edema of
the dermis in urticaria and of the subcutaneous tissue and dermis in
angioedema

Collagen bundles in affected areas are widely separated

Venules are sometimes dilated

The perivenular infiltrate consists of lymphocytes, eosinophils and

neutrophils

Elevation of plasma histamine levels with mast cell degranulation (cold

and cholinergic urticaria, exercise-related anaphylaxis)

1/3 of patients with chronic urticaria have autoantibodies to IgE or to the

chain of the FcRI
The IgE autoantibodies mediate basophil degranulation with enhancement by serum as a
source of the anaphylatoxic fragment, C5a
 DIAGNOSIS:
The distinguishing features of urticarial and angioedematous
eruptions are their rapid onset and self-limited nature

Additional characteristics are the occurrence of the urticarial

crops in various stages of evolution and the
asymmetric distribution of angioedema

Historic considerations:
Presence of specific allergens or physical stimuli
Seasonal incidence
Association with exposure to certain environments- can be confirmed by
skin testing or assay for allergen-specific IgE in serum

Absence of fever, leukocytosis and an elevated sedimentation

rate
 DIFFERENTIAL DIAGNOSIS:
HYPOCOMPLEMENTEMIA:
May reflect either an acquired abnormality attributed to the formation
of immune complexes or a genetic deficiency of CIINH

CUTANEOUS NECROTIZING ANGIITIS:

Chronic recurrent urticaria generally in females associated with
arthralgias, an elevated sedimentation rate and normo- or
hypocomplementemia

VASCULITIC URTICARIA:
Typically persists longer than 72hrs

SERUM SICKNESS:
Urticaria associated with pyrexia, lymphadenopathy, myalgia and
arthralgia or arthritis
 DIFFERENTIAL DIAGNOSIS:
HEREDITARY ANGIOEDEMA:
Suggested by a family history and a lack of pruritus and urticarial lesions, the prominence
of gastrointestinal attacks of colic, and episodes of laryngeal edema

CONTACT SENSITIVITY:
A vesicular eruption that progresses to chronic thickening of the skin with continued
allergenic exposure

ATOPIC DERMATITIS:
Presents as erythema, edema, papules, vesiculation and oozing, proceeding to a subacute
and chronic stage of scaling, fissuring and lichenification, usually involving the flexor
surfaces

CUTANEOUS MASTOCYTOSIS:
Presents as reddish brown macules and papules (urticaria pigmentosa) which urticate with
pruritus upon trauma

SYSTEMIC MASTOCYTOSIS:
Episodic systemic flushing with or without urticaria but no angioedema
 TREATMENT:
Identification of the etiologic factor(s) and their elimination

H1 antihistamines:
1st generation: Chlorphenamine, diphenhydramine
2nd generation: Loratadine, cetirizine

Cyproheptadine and hydroxyzine

Doxepine- a dibenzoxepin tricyclic compound with both H1 and H2 receptor

antagonist activity

Terbutaline or CysLT1R antagonist

Systemic glucocorticoids:
useful in the management of pressure urticaria, vasculitic urticaria, idiopathic angioedema
with or without urticaria, and chronic urticaria that responds poorly to conventional treatment

Hydroxychloroquine or colchicine- for persistent vasculitic urticaria

SYSTEMIC MASTOCYTOSIS
 SYSTEMIC MASTOCYTOSIS:
Defined by mast cell hyperplasia that in most
instances is indolent and non-neoplastic

The hyperplasia is generally recognized in:

bone marrow
Skin
GI mucosa
liver
spleen

Occurs at any age

Has a slight preponderance in males

 CLASSIFICATION of MASTOCYTOSIS:
1. CUTANEOUS MASTOCYTOSIS
Urticaria pigmentosa (UP)/ maculopapular cutaneous mastocytosis (MPCM)
Variants:
Plaque form
Nodular form
Telangiectasia macularis eruptive perstans (TMEP)
Diffuse cutaneous mastocytosis (DCM)
Solitary mastocytosis of skin

2. INDOLENT SYSTEMIC MASTOCYTOSIS (ISM)

3. Systemic mastocytosis with an associated clonal hematologic non-

mast cell lineage disease (SM-AHNMD)

4. AGGRESSIVE SYSTEMIC MASTOCYTOSIS (ASM)

Variant: Lymphadenopathic mastocytosis with eosinophilia

5. MAST CELL LEUKEMIA (MCL)

6. MAST CELL SARCOMA (MCS)

 CLINICAL MANIFESTATIONS:
Due to tissue occupancy by the mast cell mass, the tissue
response to that mass, and the release of bioactive substances
acting at both local and distant sites

Common manifestations:
Pruritus
Flushing
Palpitations
Vascular collapse
Gastric distress
Lower abdominal crampy pain
Recurrent headache

The increase in cell burden is evidenced by the lesions of

urticaria pigmentosa at skin sites, bone pain and malabsorption
 CLINICAL MANIFESTATIONS:
The mast cell-mediated fibrotic changes are limited to the liver,
spleen and bone marrow

Cutaneous manifestations:
Urticaria pigmentosa:
Reddish-brown macules or papules that respond to trauma with urtication and
erythema (Dariers sign)
Telangiectasia macularis eruptiva perstans (TEMP)
Tan-brown macules with striking patchy erythema and associated telangiectasia

Gastrointestinal manifestations:
Upper GI tract- histamine-mediated hypersecretion resulting in gastritis and
peptic ulcer
Lower GI tract- diarrhea and abdominal pain attributed to increased motility
due to mast cell mediators
Portal hypertension and ascites- due to periportal fibrosis associated with mast
cell infiltration and a prominence of eosinophils
 CLINICAL MANIFESTATIONS:
Flushing and recurrent vascular collapse:
can be aggravated by an idiosyncratic response even to a minimal
dosage of NSAIDs

Neuropsychiatric disturbances:
Impaired recent memory
Decreased attention span
migraine-like headaches

Patients may experience exacerbation of a specific

clinical sign or symptom with the following:
alcohol ingestion
use of mast cell-interactive narcotics
ingestion of NSAIDs
 CLINICAL MANIFESTATIONS:
INDOLENT SYSTEMIC MASTOCYTOSIS (ISM):
Accounts for the majority of patients
There is no evidence of an associated hematologic disorder, liver disease or
lymphadenopathy

SYSTEMIC MASTOCYTOSIS ASSOCIATED WITH CLONAL

HEMATOLOGIC NON-MAST CELL LINEAGE DISEASE (SM-AHNMD):
Prognosis is determined by the nature of the associated disorder, which can range from
dysmyelopoiesis to leukemia

AGGRESSIVE SYSTEMIC MASTOCYTOSIS (ASM):

Mast cell proliferation in parenchymal organs cause impaired liver function,
hypersplenism, and/or malabsorption
Has a poor prognosis in the absence of a hematologic disorder

MAST CELL LEUKEMIA:

Rarest form of the disease
The peripheral blood contains circulating metachromatically staining atypical mast cells
 DIAGNOSIS:
Can be established only by tissue diagnosis

Diagnosis is facilitated by bone marrow biopsy to meet the criteria

of 1 major plus 1 minor or 3 minor findings:

DIAGNOSTIC CRITERIA for SYSTEMIC MASTOCYTOSIS:

MAJOR CRITERIA:
Multifocal dense infiltrates of mast cells in bone marrow or other extracutaneous tissues with
confirmation by immunodetection of tryptase or metachromasia

MINOR CRITERIA:
Abnormal mast cell morphology with a spindle shape and/or multilobed or eccentric nucleus
Aberrant mast cell surface phenotype with expression of CD25 and CD2 (IL-2 receptor) in
addition to C117 (c-kit)
Detection of codon 816 mutation in peripheral blood cells, bone marrow cells or lesional
tissue
Total serum tryptase (mostly alpha) greater than 20 ng/mL
 TREATMENT:
H1 ANTIHISTAMINE- for flushing and pruritus

H2 ANTIHISTAMINE or PPI- for gastric acid hypersecretion

ORAL CROMOLYN SODIUM- for diarrhea and abdominal pain

ASPIRIN- for severe flushing with or without associated vascular

collapse
KETOTIFEN- alternative to aspirin in patients with gastric intolerance to NSAIDs

SYSTEMIC GLUCOCORTICOIDS- to alleviate malabsorption

TRICYCLIC ANTIDEPRESSANTS- for headaches

HYDROXYUREA- to reduce the mast cell lineage progenitors (ASM)

CHEMOTHERAPY- for frank leukemias

 ALLERGIC RHINITIS:

Hallmarks:
Sneezing
Episodic rhinorrhea
Obstruction of the nasal passages
Pruritus of the conjunctiva, nasal mucosa and
oropharynx
Lacrimation

The above symptoms occur in a temporal

relationship to allergen exposure
 PREDISPOSING FACTORS and
ETIOLOGY:
Generally presents in atopic individuals
Persons with a family history of a similar or related symptom complex and
a personal history of collateral allergy (eczematous dermatitis, urticaria
and/or asthma)

Up to 40% of patients with rhinitis manifest asthma, whereas

~70% of individuals with asthma experience rhinitis

Symptoms generally appear before the 4 th decade of life

Tend to diminish gradually with aging

The ability of allergens to cause rhinitis rather than lower

respiratory symptoms may be attributed to their large size (10
to 100 m) and retention within the nose
 PREDISPOSING FACTORS and
ETIOLOGY:
SEASONAL ALLERGIC RHINITIS:
Weeds
Grasses
Trees

PERENNIAL ALLERGIC RHINITIS:

Occurs in response to allergens that are present throughout the year
In up to of patients, no clear-cut allergen can be demonstrated as causative
Causative agents:
1. Desquamating epithelium in animal dander
2. Cockroach-derived proteins
3. Mold spores:
Molds are widespread in nature
Occur in soil or decaying organic matter
Propagate spores in a pattern dependent on climatic conditions
4. Dust/ dust mites
Dust mites are scavengers of flecks of human skin and coat the digestate with mite-specific protein for
excretion
Dermatophagoides farinae, D. pteronyssinus
 PATHOPHYSIOLOGY and
MANIFESTATIONS:

The conjunctiva is congested and edematous

Swelling of the turbinates and mucous membranes

with obstruction of the sinus ostia and eustachian
tubes precipitates secondary infection of the sinuses
and middle ear

Nasal polyps, representing mucosal protrusions

containing edema fluid with variable numbers of
eosinophils, can arise concurrently with infection within
the nasopharynx or sinuses and increase obstructive
symptoms
 PATHOPHYSIOLOGY and
MANIFESTATIONS:
NOSE:
Presents a large mucosal surface area through the

folds of the turbinates

Serves to adjust the temperature and moisture

content of inhaled air

Filters our particulate materials above 10 m in

size by impingement in a mucous blanket

Ciliary action moves the entrapped particles

toward the pharynx
 PATHOPHYSIOLOGY and
MANIFESTATIONS:
Entrapment of pollen and digestion of the outer coat by
mucosal enzymes (lysozymes) release protein allergens
(10,000 to 40,000 molecular weight)

The initial interaction occurs between the allergen and

intraepithelial mast cells and then proceeds to involve deeper
perivenular mast cells which are sensitized with specific IgE

The mucosal surface fluid contains IgA and IgE

IgE fixes to mucosal and submucosal mast cells , which

generate and release mediators through IgE-dependent
reactions that are capable of producing tissue edema with
eosinophilic infiltration
 PATHOPHYSIOLOGY and
MANIFESTATIONS:
In sensitive individuals, the introduction of
allergen into the nose is associated with:
Sneezing
Stuffiness
Nasal discharge containing histamine, PGD2 and
leukotrienes

Biopsy specimens of nasal mucosa show

submucosal edema with infiltration with
eosinophils, along with some basophils and
neutrophils
 DIAGNOSIS:
Depends on an accurate history of occurrence
coincident with pollination of the offending agent

Differential diagnosis:
Structural abnormalities of the nasopharynx
Exposure to irritants
Upper respiratory infection
Pregnancy with prominent nasal mucosal edema
Prolonged topical use of -adrenergic agents in the form
of nose drops (rhinitis medicamentosa)
Use of certain therapeutic agents (-adrenergic
antagonists, estrogens)
 DIAGNOSIS:
Peripheral eosinophilia

Total serum IgE is elevated, but the

demonstration of immunologic specificity
for IgE is critical to an etiologic diagnosis

Skin testing:
Intracutaneous or intradermal

ELISA
 TREATMENT:
Allergen avoidance- the most cost-effective means of
managing allergic rhinitis

H1 antihistamines:
Effective for nasopharyngeal itching, sneezing, watery rhinorrhea, and
ocular manifestations as itching, tearing and erythema
Less lipophilic, and their ability to cross the blood-brain barrier is
reduced
Has minimal sedating and anticholinergic side effects
Examples:
Fexofenadine
Loratadine
Desloratadine
Cetirizine
Levocetirizine
Azelastine
 TREATMENT:
-adrenergic agents:
Generally used topically to alleviate nasal congestion and obstruction
Examples:
Phenylephrine
Oximetazoline
Oral -adrenergic agonist decongestants containing pseudoephedrine
in combination with antihistamine to manage nasal congestion
Contraindications: narrow angle glaucoma, urinary retention, severe
hypertension, marked CAD

Cromolyn sodium nasal spray

Intranasal high-potency glucocorticoids- most potent

Examples: beclomethasone, flunisolide, budesonide, fluticasone,
mometasone
 TREATMENT:
Topical ipratropium- an anticholinergic agent effective in reducing rhinorrhea

Immunotherapy (hyposensitization)
Consists of repeated subcutaneous injections of gradually increasing concentrations of the
allergen(s) considered to be specifically responsible for the symptom complex

Duration of treatment: 3-5 years

Discontinued based on minimal symptoms over 2 consecutive seasons of exposure

Contraindicated in patients with:

Significant cardiovascular disease
Unstable asthma

Caution in patients requiring -adrenergic blocking therapy

Reserved for clearly documented seasonal or perennial rhinitis, clinically related to defined
allergen exposure with confirmation by the presence of allergn-specific IgE
 TREATMENT:
Stepwise management of seasonal or perennial rhinitis:

(1) identification of the offending allergen(s) by history and

confirmation of the presence of allergen-specific IgE by skin test and/or
serum assay

(2) avoidance of the offending allergen

(3) medical management

(a) mild intermittent symptoms- oral or intranasal antihistamines,intranasal cromolyn
prophylaxis

(b) moderate to severe symptoms- intranasal glucocorticoids plus oral antihistamines

or antihistamine-decongestant combinations

(c) persistent symptoms- intranasal or oral (prednisone) glucocorticoids, oral

antihistamine-decongestantcombinations, topical ipratropium, allergen-specific
immunotherapy