Clinical features of allergic rhinitis and skin prick test analysis based on the ARIA classification: a preliminary study in Malaysia.
ABSTRACT Allergic rhinitis (AR) is a prevalent disease worldwide but is still underdiagnosed in many parts of Asia. We studied the clinical profiles of AR patients in our community based on the new ARIA classification and investigated the aetiological allergens using a skin prick test.
In 2008, 142 newly diagnosed patients with AR were seen and underwent skin prick testing with 90 patients completing the study.
Intermittent mild and moderate/severe AR were evident in 10% and 21.1% of the patients, while persistent mild and moderate/severe were seen in 20% and 48.9%, respectively. Rhinitis and asthma co-morbidity occurred in 28.8% with asthma incidence significantly higher in persistent AR (P = 0.002). There was no significant association between AR severity, city living and asthma co-morbidity. Nasal itchiness and sneezing were the main presenting complaints and were more common in intermittent AR (P <0.05). Sleep disturbance was associated with moderate-severe AR (P <0.05). Polypoidal mucosa was associated with asthma co-morbidity (P <0.05). Monosensitivity reaction occurred in 12.2% of patients and was associated with fungi sensitivity (P <0.05). Majority of patients were oligosensitive (52.8%) and polysensitive (34.4%) and were significantly associated with moderate-severe persistent AR (P <0.01). The highest positive skin prick reaction and the largest average wheal diameter were for the house dust mites and cat allergen (P <0.05).
Our results reflected the AR profiles in our country, which was comparable with typical profiles of the neighbouring country and other Mediterranean countries with a similar temperate climate.
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Analysis of Allergic Rhinitis in Malaysia based on the ARIA Classification—Zamzil Amin Asha’ari et al
Original Article
Clinical Features of Allergic Rhinitis and Skin Prick Test Analysis Based on the
ARIA Classification: A Preliminary Study in Malaysia
Zamzil Amin Asha’ari,1MMed (ORL-HNS), Suhaimi Yusof,2MMed (ORL-HNS), Rushdan Ismail,3MMed (ORL-HNS), Che Maraina Che
Hussin,4M Path
1 Department of Otolaryngology-Head & Neck Surgery, International Islamic University Malaysia, Jalan Hospital, 25100 Kuantan, Pahang
2 Department of Otolaryngology-Head & Neck Surgery, Hospital Tengku Ampuan Afzan, 25100 Kuantan, Pahang
3 Department of Otolaryngology-Head & Neck Surgery, School of Medical Sciences, Hospital Universiti Sains Malaysia, 15160 Kubang Kerian, Kelantan
4 Department of Immunology, School of Medical Sciences, Hospital Universiti Sains Malaysia, 15160 Kubang Kerian, Kelantan
Address for Correspondence: Dr Zamzil Amin Asha’ari , Department of Otolaryngology-Head & Neck Surgery, International Islamic University Malaysia,
Jalan Hospital 25100 Kuantan, Pahang, Malaysia.
Email: zamzilamin@yahoo.com
Abstract
Introduction: Allergic rhinitis (AR) is a prevalent disease worldwide but is still underdiag-
nosed in many parts of Asia. We studied the clinical profiles of AR patients in our community
based on the new ARIA classification and investigated the aetiological allergens using a skin
prick test. Materials and Methods: In 2008, 142 newly diagnosed patients with AR were seen
and underwent skin prick testing with 90 patients completing the study. Results: Intermittent
mild and moderate/severe AR were evident in 10% and 21.1% of the patients, while persistent
mild and moderate/severe were seen in 20% and 48.9%, respectively. Rhinitis and asthma
co-morbidity occurred in 28.8% with asthma incidence significantly higher in persistent AR
(P = 0.002). There was no significant association between AR severity, city living and asthma
co-morbidity. Nasal itchiness and sneezing were the main presenting complaints and were more
common in intermittent AR (P <0.05). Sleep disturbance was associated with moderate-severe
AR (P <0.05). Polypoidal mucosa was associated with asthma co-morbidity (P <0.05). Mono-
sensitivity reaction occurred in 12.2% of patients and was associated with fungi sensitivity (P
<0.05). Majority of patients were oligosensitive (52.8%) and polysensitive (34.4%) and were
significantly associated with moderate-severe persistent AR (P <0.01). The highest positive
skin prick reaction and the largest average wheal diameter were for the house dust mites and
cat allergen (P <0.05). Conclusion: Our results reflected the AR profiles in our country, which
was comparable with typical profiles of the neighbouring country and other Mediterranean
countries with a similar temperate climate.
Ann Acad Med Singapore 2010;39:619-24
Key words: Allergic rhinitis, ARIA classification, Malaysia, Skin prick test
Introduction
Allergic rhinitis (AR) is a common disease worldwide
and is known to cause serious implications to the physical
and mental health status of the individual sufferer. It
also impacts significantly on healthcare expenditure. For
instance, the direct costs of allergic rhinitis in the United
States (US) alone were approximately 2.7 billion dollars
a year.1 Nearly 3.8 million days of both work and school
were also lost annually due to the disease.1
Despite a major health and financial concern, AR is
still underdiagnosed and undertreated in many countries.2
Epidemiological data on the Asian population are sparse. In
Malaysia, published studies only focused on a limited age
group and there was no epidemiological study in accordance
with the recent ARIA (Allergic Rhinitis and its impact on
Asthma) classification.3 The ARIA guidelines subdivide AR
based on the duration/chronicity of symptoms (Intermittent
for symptoms <4 days/week or <4weeks/year or Persistent
for symptoms >4 days/week and >4 weeks/year) and grading
of severity (mild when symptoms do not impair sleep,
daily activities and work/school performance or moderate/
severe when symptoms impair sleep, daily activities and
work/school performance).2,4 This new classification was
found to yield better treatment outcomes for AR patients.5
Skin prick test is the most widely used and is regarded
as the gold standard diagnostic test in allergy. We aimed
to study the clinical profiles of AR patients in accordance
with the new ARIA guidelines and to investigate
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Analysis of Allergic Rhinitis in Malaysia based on the ARIA Classification—Zamzil Amin Asha’ari et al
common aetiological allergens in our community from a
skin prick test.
Materials and Methods
The study was conducted over one year’s duration (2008).
The source population was from new patients attending
the AR clinic in a tertiary referral hospital in Malaysia. All
patients aged more than 18 years old with positive history
of allergy (3 or more recurrent symptoms of rhinorrhea,
sneezing, nasal blockage and nasal itchiness during the last
12 months) were invited to participate in the study. The
patient’s detailed history and nasal endoscopic examination
were carried out, and another appointment was given for
the skin prick test 2 weeks later. Those patients who are
on antihistamines were asked to stop treatment at least one
week prior to the skin prick test. Informed written consent
was obtained from all patients. The study protocol was
approved by the Research and Ethics Committee of the
hospital.
Skin prick test were done by the same investigator. Eight
common allergens in our community were used for the
skin prick test, namely, Dermatophagoides pteronyssinus
(house dust mite), Felis domesticus (domestic cat), Mucor
mucedo (fungi), wheat flour, peanut, egg yolk, egg white
and chicken meat. Numbered strips (2 cm apart) were
applied onto the forearm area. Drops of selected allergen
were then placed on the forearm skin next to the numbered
strip. A sterile lancet (ALK-Abello skin prick test kit, Bege
Alle, 2970 Horsholm, Denmark) was used to prick the skin
gently through the drops of allergen. Excess allergen was
then wiped off. Histamine (as positive control) and diluents
(as negative control) were included in the test. After 20
minutes, the forearm skin was examined and the wheal and
flare sizes were measured in 2 perpendicular directions. The
presence of a wheal of at least 3 mm and flare of at least
10 mm larger than the negative control were regarded as
a positive reaction. Patients with a negative skin prick test
were excluded from the study.
The data obtained in this study were classified according
to the ARIA guidelines and analysed using SPSS 13
software (Chicago, Illinois). The chi-square test or Pearson
correlation was used whenever appropriate to evaluate
statistical analysis, where P value of less than 0.05 was
considered significant.
Results
A total of 142 new patients (90 females, 52 males) with
AR were seen in the allergic clinic, HUSM in 2008. Out
of this, 90 patients were enrolled into the study. Their age
group ranged from 18 to 66 years old with the mean age
of 32.6 years. Fifty-five patients (61.1%) are female. The
majority of the study population were Malay, which account
for 76.7% (n = 69 ), followed by Chinese at 15.6% (n = 14),
Indian at 1.1% (n = 1) and others at 6.6% (n = 6). In terms of
occupation, the majority of the study subjects (27.8%) were
students, followed by housewives (24.4%), professional
workers (13.4%), teachers (10%), retirees (5.6%) and the
rest were either odd job workers or unemployed. Sixty-
three (70%) of the patients were living in the urban area
of Kota Bharu, a city with more than 300,000 total number
of inhabitants.
Table 1 summarises the main clinical features of the
patients. From history taking, 26 (28.8%) patients have a
concomitant history of asthma and were on bronchodilator
inhalers. Of these numbers, 24 of them had Persistent AR
from the ARIA classification. Asthma co-morbidity was
significantly associated with Persistent AR (P = 0.002).
Table 1. Clinical Characteristics of the Study Subjects (n = 90)
ARIA Classification
Mild intermittenta 9 (10.0%)
Moderate-severe intermittent 19 (21.1%)
Mild persistentb
18 (20.0%)
Moderate-severe persistent 44 (48.9%)
Smoking status
Active 13 (14.4%)
Former 5 (5.6%)
Never 72 (80%)
Associated morbidity
Asthma 26 (28.8%)
Dermatitis 8 (8.8%)
Conjunctivitis 12 (13.3%)
Family history of atopy 49 (54.4%)
Trigger allergen (from history)
Dust 83 (92.2%)
Food 44 (48.9%)
Air-conditioned room 20 (22.2%)
Domestic pet 20 (22.2%)
Drugs 13 (14.4%)
Symptoms
Nasal itchiness 78 (86.7%)
Sneezing 74 (82.2%)
Rhinorrhea 62 (68.9%)
Nasal blockage 60 (66.7%)
Eye irritation 52 (57.8%)
Sleep disturbance 39 (43.3%)
aIntermittent: symptoms <4 days/week or <4 consecutive weeks
bPersistent: symptoms >4 days/week or >4 consecutive weeks
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There was no significant association between AR severity
and the presence of asthma (P >0.05). Twenty out of 26
patients were living in the city. However, there was no
association between city living and AR with asthma co-
morbidity (P = 0.361). More than half of the cases (n =
49 , 54.4%) had positive family history of atopy but there
was no association seen between positive family history
and the chronicity of AR (P = 0.89) or the severity of the
disease (P = 0.22).
Eighty-three (92.2%) of the study subjects admitted that
their allergic symptoms were triggered by exposure to a
dusty environment. Forty-four patients (48.9%) have food
allergies and 20 patients (22.2%) admitted to having an
allergy triggered by contact with their domestic pets. The
most common (97.7%) food type that triggered allergy
was seafood-based particularly, prawn and anchovy sauce,
followed by chicken-based food (meat, egg and paste).
There was no association seen between the type of trigger
allergen and the ARIA classification of the disease (P >0.05).
Nasal itchiness and sneezing were the two main clinical
presentations. The mucosal irritation symptoms (nasal/eye
itchiness and sneezing) were significantly more common in
Intermittent AR (P <0.05) (Table 2). Sleep disturbances were
reported mostly by patients with moderate-severe diseases,
regardless of the persistent or intermittent types (P <0.001).
Among the common endoscopic findings in our patients were
inferior turbinate hypertrophy (75.6%), mucoid discharge
(55%), mulberry turbinates (22%) and polypoidal nasal
mucosa (16%). The presence of a polypoidal mucosa was
significantly associated with asthma co-morbidity (P <0.05).
Table 3 summarises the distribution of skin prick test
reactivity according to the ARIA classification. Majority
fell into Persistent AR (62/90, 68.9%), with the highest
within the moderate-severe group (44/90, 48.9%). Of the 90
patients, 12.2 % (n = 11) had positive skin reaction to one
reagent (monosensitive) and the majority were those with
sensitivity to Mucor mucedo (P <0.05). The majority of our
subjects were in the oligosensitive group (53.3%, n = 48)
and this comprised mainly of those who were sensitive to
the house dust mites and cat (P <0.001). Statistical analysis
also showed that the moderate-severe persistent group has
the highest positive skin reaction to more than one reagent
(oligo-polysensitive) (P <0.01).
Mean diameter of the wheal and the prevalence of
positive skin prick test are shown in Table 4. The largest
mean diameter was for the house dust mite (3.87 mm) and
Table 2. Prevalence of the Clinical Symptoms According to ARIA Classification
Clinical symptoms Intermittent (n = 28) Persistent (n = 62) Total (n = 90)
Mild (n = 9)
Moderate-severe
(n = 19)
Mild (n = 18)
Moderate-severe
(n = 44)
Nasal itchiness 9 19 16 34 78
Sneezing 9 19 12 34 74
Rhinorrhea 6 12 16 28 62
Nasal blockage 3 8 6 43 60
Eye irritation 8 18 6 20 52
Sleep disturbance 0 13 1 26 39
Table 3. Distribution of Skin Prick Test Reactivity According to the ARIA Classification
ARIA classification Positive skin prick test (n = 90) Total
One allergen
(monosensitive)
2 allergen
(oligosensitive)
3 or more allergen
(polysensitive)
Mild intermittenta
4 2 3 9 (10.0%)
Moderate-severe intermittent 4 10 5 19 (21.1%)
Mild persistentb
2 15 1 18 (20.0%)
Moderate-severe persistent 1 21 22 44 (48.9%)
Total 11 (12.2%) 48 (52.8%) 31 (34.4%) 90 (100%)
aIntermittent: symptoms <4 days/week or <4 consecutive weeks
bPersistent: symptoms >4 days/week or >4 consecutive weeks
χ2:14.172, df 3(oligosensitive and polysensitive groups were evaluated as one), P <0.01 Monte Carlo Exact.
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the smallest diameter was for the egg white (1.13 mm).
The diameter of wheal is correlated with the positivity of
the results (P <0.05). House dust mite yielded the highest
number of positive results (80.0%), followed by cat (37.8%)
while chicken meat was the lowest at 8.9% (P <0.05).
Discussion
AR is a highly prevalent disease affecting 20% of the
general population in developed countries.6-8 AR is still
under-diagnosed and under-treated in many parts of Asia
despite a high prevalence of 18% to 44% proposed.9,10 In
Malaysia, a study in the paediatric community showed
the overall incidence of rhinitis symptoms at 27%, with
a significantly higher prevalence in the 12 to 14 year-old
age group (38.2%) than in the 5 to 7 year-old age group
(18.2%).11 Subsequent study in the same population 6 years
later found no major changes in the prevalence rate of AR,
indicating that the disease remains at a high prevalence rate
as before.3 No data were found for the adult population with
AR here. With our country gearing towards a developed
nation, we may be facing a higher incidence of AR patients
in the near future.
The present study was carried out in a tertiary referral
hospital in the North-Eastern part of Malaysia, which caters
for almost half a million of population. A total of 142 new
adult patients were seen in the AR clinic throughout the
year of study. Out of this number, 90 patients (63.4%) are
female, reflecting a slight female predominance in our
adult AR patients. There were not many studies which
have looked into the gender preponderance of AR. A multi-
centre epidemiological study showed that the prevalence is
approximately equal between men and women.12 However,
they found that in children, AR is more common in boys than
in girls. In the geriatric population, rhinitis is less commonly
Table 4. Mean Diameter (mm) of Wheal in the Skin Prick Test and the
Prevalence of Positive Skin Prick Results (n = 90)
Type of allergen
Wheal diameter
Mean ( SD )
Positive
results n (%)
Significance
Cat
1.79 ( 1.14 )
34 ( 37.8 )
χ2:4.373,df1,
P <0.05
Wheat flour 1.39 ( 0.88 ) 18 ( 20.0 ) P >0.05
House dust mite
3.87 ( 2.54 )
72 ( 80.0 )
χ2:134.098,df1,
P <0.001
Mucor mucedo 1.51 ( 0.99 ) 18 ( 20.0 ) P >0.05
Peanut 1.22 ( 1.06 ) 23 ( 25.6 ) P >0.05
Egg yolk
1.23 ( 0.94 )
16 ( 17.8 )
χ2:5.776,df1,
P <0.05
Egg white
1.13 ( 0.94 )
16 ( 17.8 )
χ2:5.776,df1,
P <0.05
Chicken meat
1.16 ( 0.78 )
8 ( 8.9 )
χ2:19.369,df1,
P <0.001
allergic in nature, supported by a study that showed the total
and specific serum IgE was significantly decreased with
age in 559 patients with atopy.13 This probably explained
why the majority of our AR patients fell into a younger age
group with the mean age of 33 years.
The majority of the patients in this study were Malays
(76.7%), followed by Chinese and Indians. However,
these figures did not reflect the actual ethnic distribution
of a predominant Malay race at 90% to 95% in the study
area. Thus, the high number of Chinese patients with AR
here may suggest that AR is also racially distributed, or
otherwise it simply showed that the awareness to seek
treatment is higher in the Chinese than the Malay patients.
There is no such study yet in Malaysia that compares the
racial distribution of the disease so no definitive conclusion
can be made from this.
Environmental pollution can trigger the symptoms of AR,
thus the type of occupation plays an important role in the
control of the disease. The highest number of our patients
was students. Students fall into a younger age group of
below 25 years old, so a high number of students in this
study can be explained by the higher prevalence of AR in
the younger age group. Housewife was the second highest
occupational group in our study sample. The majority of
persistent aero-allergens in our environment were found
indoors, and these housewives spent most of their time in
the house hence they were more exposed to the allergens.
Majority (70%) of our patients lived in the city. Here,
although city living does not correlate to the chronicity
and severity of our AR patients, other studies in the West
have shown that rural residence was negatively correlated
with allergen sensitivity, particularly to pollen.14,15 The
difference in the climate and seasonal changes may explain
the discrepancy between our result and theirs.
AR and allergic asthma are both atopic diseases, with
inherited tendency to develop IgE immune response. Both
AR and asthma can be triggered by the same allergen and
frequently coexist.16 Asthma is a clinical diagnosis that
incorporates genetic predisposition and clinical symptoms
with objective measures of lung function, and in this study,
the asthmatic subjects were already confirmed by the
respiratory physicians and are already on treatment for
it. In our study, 28.8% of our AR subjects had concurrent
asthma and there was a significant association between
asthma co-morbidity and the chronicity of the disease in
the ARIA sub-division (higher in Persistent type). A recent
study showed a higher prevalence of asthma co-morbidity
at 45.3%, but they only found a significant association
between asthma and the older AR classification (seasonal
and perennial), and not with the new ARIA classification.14
Differences in research methodology, criteria of patient
selection and sample size may explain the dissimilarity of
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Analysis of Allergic Rhinitis in Malaysia based on the ARIA Classification—Zamzil Amin Asha’ari et al
the findings. Despite this, our results are consistent with
others in that we noted that the severity of the AR according
to ARIA classification did not correlate with the presence
of asthma symptomatology.14,17 In our patients with both
diseases, rhinitis precedes asthma in 77% of the cases. This
finding is also in agreement with another study.18
In the present study, 54.4% of the subjects had a similar
history of atopy among the family members. Family
history of allergy is the single-most important factor for
the development of allergic diseases. Adults with a family
history of asthma or rhinitis have a two-fold to six-fold
risk of developing AR compared with adults without such
a family history.19 Borish20 in1999 reviewed studies on
the inheritance of allergic diseases and summarised that
up to 50% of children who have one parent and up to
75% of children who have both parents with atopy could
become atopic. Similar to other studies, we also found that
positive family history did not correlate to the chronicity
and severity of AR.14,19,20
Aero-allergens like dust-mites, pollens and animal
dander are responsible for many sensitivity reactions in
AR patients. The high incidences of asthma co-morbidity
in AR patients are partly due to the same sensitivity to
these aero-allergens. In our study, we found almost half of
the AR patients also had food sensitivity from the history.
The most common type of food sensitivity in these patients
was towards seafood-based, followed by chicken-based
food. Living near the coastal region, seafood with rice
is the main diet in the study population and this could be
the reason for the high reported seafood sensitivity levels
here. Of particular interest, the seafood type that most
commonly induced allergy was the anchovy sauce. This
is a local favorite sauce eaten by the majority of people in
the study area with rice. Food sensitivity in AR patients is
less well studied and there were few publications available
for analysis and comparison. One study in Southeast Asia
showed a high prevalence of crustacean seafood sensitivity
in the general population.21 A high incidence of seafood
sensitivity in our AR patients could be better studied using
a proper specific seafood derived allergen. Unfortunately,
we did not have them in our skin prick study.
The ARIA guidelines were used to define the diagnostic
criteria for AR in this study.2,4 AR is defined as a symptomatic
disorder of the nose characterised by one or more of the
symptoms of itchiness, sneezing, rhinorrhea and nasal
congestion, which are reversible spontaneously or with
treatment. Other symptoms may also be present, such as eye
and sleep symptoms. Although symptoms of AR are clearly
defined, very few studies have analysed the prevalence
of each of the symptoms. Aidan et al22 did a survey on
1000 AR patients assessing the impact of the individual
symptoms. They found that most of their patients complaint
of nasal blockage (85%), followed by sneezing (63%), eye
itchiness (60%), rhinorrhea (56%), watery eyes (51%) and
nasal itchiness (41%). We, however, found that the highest
presenting symptom in our patients was nasal itchiness,
followed by sneezing, rhinorrhea and nasal blockage.
Environmental, genetic or different allergen profiles may
have contributed to the dissimilarity of the symptoms, as
it was shown that these factors influenced the sensitivity
reaction even within the same geographical region.23 In our
study, the severity of AR is best represented by the sleep
disturbance symptom as it was significantly associated
with a more severe AR regardless of the type. This is in
accordance with other studies and the ARIA guidelines.14,24
Our result also agreed with Anastassakis et al14 who found
that mucosal irritation symptoms were more common in the
less chronic (seasonal) type of rhinitis. On the other hand,
nasal endoscopic examination in our patients revealed a
high number with inferior turbinate hypertrophy, mucoid
discharge, mulberry turbinates and polypoidal mucosa.
These findings indicated the chronicity of our patients’
diseases and possibly also reflected poor compliance to the
medications and treatments prescribed. Polypoidal mucosa
was found significantly associated with asthma co-morbidity
in line with Samter’s syndrome (P <0.05).25
Two-thirds of our AR patients fell into a Persistent type
(Tables 1 and 3). This finding seems to agree with studies
within Asian and Southern Mediterranean countries
with warmer climates.2,9,26 Our country’s constant high
temperature and humid conditions resulted in persistently
high concentration of indoor and outdoor allergens
throughout the year. This will lead to the prevalence
of chronic sensitivity reactions in patients with AR.
Monosensitivity occurred in 12.2% of our patients, the
highest with sensitivity to fungi (P <0.05). This similar
result has been reported in a high temperature-high humidity
climate study.14 Possible explanation is that the two areas
were similar in terms of being agricultural areas, besides
having the same type of climate. Our paddy field may be
similarly infected with fungi as the other cotton plantation
which might then be responsible for the results. On the other
hand, the majority of our patients were the oligo-sensitive
type. Dust mites and cat allergen were responsible for the
significant number of such patients with oligo-sensitivity
(P <0.001). House dust mites and animal dander are the
best described persistent indoor allergens and our warm
and humid tropical climates are favourable conditions for
them to thrive. In our skin prick test, house dust mites had
the largest average wheal diameter and the highest positive
results among all studied allergens. The prevalence of a
positive skin prick test for cat is second highest after house
dust mite. Cat allergen is found in the saliva and skin hair
follicles. Cat allergen is particularly frustrating because