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Pathophysiology and Diagnostic Procedure in Allergic Rhinitis

By :
Iwin Sumarman
Faculty of Medicine Padjadjaran University
Dr. Hasan Sadikin General Hospital
Bandung - Indonesia
Chronic ongoing disease Factors :
- Environmental (allergenic and or nonallergenic)
- Genetics
- Immunity distrubances
- Suceptible to secunder infections
Distribution of PAR (symptoms in Indonesia
Symptoms
1)
2)
3)
Stage 2+3+4 Stage 3+4
Rhinorhea
98,1 55,0
80,2
41,8
Sneezing
97,6 53,3
87,1
46,4
N Congestion
47,4 30,0
52,3
15,3
N Itching
18,7 26,7
nd
nd
Adapted from:
1) Sumarman et al. Hasan Sadikin Hosp. ENT-OPD patients (Bandung, 1992)
2) Suprihati et al Karyadi Hosp. ENT-OPD patients (Semarang, 1983)
3) Haryanto & Sumarman. (Population of Bandung City, 1999)
Allergic Rhinitis
DIAGNOSTIC Procedure:
-

History of Nasal & non nasal symptoms


History of Family Allergy
Nasal & Non nasal clinical signs
Adjunct diagnostic

The potential treatment modalities of Allergic Rhinitis management:


Three basic approach:
1. Allergen avoidance
2. Pharmacotherapy

3. Immunotherapy
(WHO Initiative ARIA 2000
Optional therapy:
Pharmacotherapy and/or surgery for complications Either diagnostic or management
of allergic rhinitis, present or future, needs a good understanding of allergic rhinitis
phatophysiology

Pathophysiology of Allergic Inflammation


Three phases :
Sensitization phase
Early Phase Allergic Reaction
Late Phase Allergic Reaction

Other important molecular products during Early- and Late-Phase Allergic


Reactions :
Adhesion molecules :

Immunoglobulin gene superfamily :


ICAM-1, ICAM-2, VCAM-1

Selectin gene superfamily


E-selectin, P-selectin, L-selectin

Integrin family:
LFA-1, Mac-1, p150,95, VLA-4, VLA-6, Act-1
8 Adhesion molecules functions :
VCAM-1 (especially for EOS cells)
ICAM-1 and E-selectin (for EOS, Baso and Neutro cells)
Adhesion molecules functions on recruitment of inflammatory cells :

Blood vessel

Eos
in
air
cavi
ty

Eos
inTis
sue

1. Rolling (Ig superfammily and integrin)


2. magination (Ig superfammily and integrin)
4. Diapedesis (L-selectin)
4 and 5. Chemotaxis (Ig superfammily and integrin)

Alergy Rhinitis
Symptoms:
* Rhinorrhea * Sneezing
* Congestion * Nasal Itchy
1 = trivial ; 2 = mild;
3 = moderate; 4 = severe
Sneezing Predominantly in EPR

(1-2 minutes after allergen exposure)

Is associated with mast cells degranulation:


Histamine stimmulation on H1 receptor on C fibre sensory nerve ending

Peptide endotelin-1

Leukotrien
Pruritus
Exclusively in EPR
Nasal itching and Palatal clicking
Histamine stimmulation on H1 receptor on C fibre
sensory nerve ending
Protaglandin may also constribute
Rhinorrhea
Excessive discharge from nasal mucous. membrane
Begin 3 min., last for approx. 20 to 30 min. after alergen challenge
Rhinorrhea (Histamine release from Mast cells)

Predominantly in EPR, can also in LPR


Effect of :

Histamine on H1 receptor:

Leak of plasma and large molecular-weight of proteins

Glandular stimulation through parasympathetic nerve

Acetylcholine

LTC4, LTD4, and LTE4, Bradikinin, PGD2, neuropeptide (SP, VIP


Congestion :
Sensation of increase resistance to air flow within the nose
Vascular obstructive event (dilatation) (non fix obstruction):
Histamine-H1-receptor-mediated-vasodilatation But, Histamine is a minor factor
and only during EPR Mayor factors are:
l PGD2, LTC4, LTD, PAF (vasodilatation mayor factors)
PGD2: 10 X histamine effects
l Bradykinin-bradykinin 2 receptor
l Neuropeptide (SP, calcitonin-gene related peptide)
Alergy rhinitis
DIAGNOSTIC Procedure:
Routine tests:(according to WHO initiative ARIA 2000)
Nasal symptoms: 1. Sneezer and runners 2. Blockers (Rhinorrhea
Sneezing Congestion- Nasal Itchy)
History of non-nasal allergic symptoms (pharynx, ear, eye, skin, lung)
History of Family Allergy
External Nasal & internal nasal clinical signs
Non nasal clinical allergic signs
Bandung AR classification
Perenial allergic rhinitis Occupational allergic rhinitis Seasonal allergic rhinitis
Staging or Allergic Rhinitis
Total nasal symptoms score:
(for rhinorhea, sneezing, congestion, nasal itching)
Stage I (Trivial)
1-3
Stage II (mild)
4-6
Stage III (moderate)
7-9
Stage IV (severe)
10 - 12
New Classification of AR (according to WHO iitiative ARIA 2000):
Intermitten : the symptoms are present:

< 4 days a week

Or for less than 4 weeks

Persistent : the symptoms are present:

> 4 days a week

And for more than 4 weeks


New AR symptoms grading classification (according to WHO initiative ARIA 2000):
Mild : that none of the following items are present:

Sleep disturbances

Impairment of daily activity, leisure and/or sport

Impairment of school or work

Trouble some symptoms


Moderate Severe :
One or more of the following items are present:

Sleep disturbances

Impairment of daily activity, leisure and/or sport

Impairment of school or work

Trouble some symptoms


DIAGNOSTIC Procedure:
Routine tests:(according to WHO initiative ARIA 2000)
Allergy tests
* Skin test and or
* Serum specific IgE)
Endoscopy
* rigid or * flexible
Nasal secretion (cytology)
Nasal challenge ( * allergen * lysin aspirin )
Radiology (plain radiographs and or CT-scan
DIAGNOSTIC Procedure: Optional tests:(according to WHO initiative ARIA
2000)
Nasal biopsy
Nasal swab bacteriology
Radiology MRI
Mucociliary function
Nasal airway assessment
Olfaction tests
Nitric oxide meassurement
Skin Tests

Scratch test
Patch test
Intracutan test
Skin prick test

Skin endpoint titration (SET)

Each test has own advantages and disadvantages and specific indication
Skin Prick Test
- Indonesian : Tes kulit tusuk (Tes kulit cungkit)
- Simple, save, painless, and preferably
- Single device (good enough and cheap)
- Multiple devices (better but more expensive)
- Volar region
- The prick be placed > 3 cm apart
Standardized extract
The best set: 6 allergen, but can more
No prick bleeding (in appropriate result)
Assesment: diam. wheal and flare (mm) (0, 1+, 2+, 3+ and 4+)

False negative > positive

Skin endpoint titration (SET)

Indications:

If SPT negative
ID test
SET

For determinining IT allerg. starting dose

Extract mite 1:100; other 1:20 (Standardized extract)

Dilution 1 : 5 (Mite #1=1:500; #5=312.500) (Other Alg: #1=1:100;


#5=62.500)

Upper hand region, be placed > 5 cm apart


Assesment: diam. wheal (mm)

wheal 0 = 4mm
wheal 15 < 5 mm (Negative resp)
wheal 15 > 5 mm (Positive resp)

SET interpretation
The endpoint is the next stronger dilution with a > 2mm larger wheal positive
response
0 minute wheal : 4 mm
15 minutes wheal:
#5
#4
#3
#2
# 1 Dilution
Normal response
5

7
9 mm
Endpoint is # 3
Abnormal response:
Flash response; Plateau response; Hourglass response Skin endpoint titration (SET)
The ultimate objective of SET are:
1. Safe initiate dose of immunotherapy (IT)
2. Decrease of interval of injection of IT
3. Usefull at prae seasonally or co-seasonally IT
4. Safe testing and treatment on patient with severe symptoms

The advantages and disadvantages of in vitro test Imunoglobulin E (IgE)


Does not mediate the allergic alone
sensitized to miscellaneous antigens (not specific)
IgE RAST (0, 1+, 2+, 3+, 4+)
IgE modified RAST (0, 1+, 2+, 3+, 4+)
Specific to one antigen/allergen
But expensive
CONCLUSIONS :
1.
Allergic rhinitis is IgE mediated hypersensitivity,
starting by sensitization phase, followed by EPR and LPR
2. During LPR : inflammatory cells accumulation followed by mediators,
cytokines, chemokines release (including adhesion molecules and chemotactic
factors)
3. Adhesion molecules play an important role on rolling and margination,
diapedesis, and chemotaxis of inflammatory cells
4. Well understanding of AR pathophysiology is important for selecting either
rational present diagnosis or treatment strategies
5. Well understanding of AR pathophysiology is more important for searching
either future diagnotic or treatment strategies (eg. Recombinant allergens
6. The WHO initiative ARIA 2000 has lay down the rational concept of
diagnotic strategies: the routine tests and the optional tests.