Introduction

Allergy is a disorder of the human immune system which causes an abnormal or intense reaction to any harmless substance present in the environment.^[1] T2 helper white blood cells on contact with an allergen, produce Immunoglobulin E (IgE) antibody which is specific to a particular allergen. Re-exposure to the same allergen, triggers the release of inflammatory chemicals such as histamines, leukotrienes leading to allergy symptoms. Allergic reactions are characterized by the involvement of allergen specific IgE in anaphylaxis, allergic rhinitis, some food allergies, and allergic asthma.^[2] Prevalence of allergic disease in India is 20 to 30% of the total population and mainly comprises of asthma, rhinitis, drug, food and insect allergy, eczema and urticaria. Prevalence of bronchial asthma was found to be 2.05% as per Indian study on Epidemiology of Asthma, Respiratory Symptoms and Chronic Bronchitis (INSEARCH).^[1] Besides asthma, there is a rising trend of atopic rhinitis, anaphylaxis, drug, food and insect allergy, eczema, urticaria, and angioedema in India.^[3] Certain studies showed that IgE-mediated food allergy affects as many as 6-8% children and 3-4% of adults.^[4] Prevalence of atopic dermatitis in adults was found to be 10.2%.^[5] Not all of the risk factors for allergy are known, but genetic and environmental factors are of importance besides lifestyle factors.^[6] Some common triggers for inhalant allergies are advancing age, smoking, tobacco exposure, family history of asthma, use of cooking fuels indoor allergens, outdoor allergens and air pollution.^[1], ^[7] Asthma management in India remains poor leading to higher morbidity and a poor quality of life. 40-50% of paediatric asthma cases in India are uncontrolled or severe.^[8]

Total IgE is used as a screening test for allergy. Its elevated levels are seen in allergic as well as non-allergic diseases. When combined with allergen specific IgE, it gives a comprehensive testing solution.^[6] However, Total IgE has a low diagnostic efficiency, therefore ImmunoCAP ImmunoCAP Phadiatop is used as a screening method for patients without a history of allergy thus reducing the number of patients that must be referred for allergen-specific diagnostic testing.^[9] Phadiatop is a qualitative assay and indicates whether patients are IgE sensitized with common inhalant allergens. Phadiatop has a high efficiency in screening of patients without a history of allergy to confirm diagnosis of atopy thus reducing the number of patients referred for allergen specific testing.^[9] Immuno CAP can be performed irrespective of a patient’s age, skin condition, medication, symptom, disease activity, pregnancy, and even in early infancy.

India is the most diverse country in the world with respect to religions, languages, food, clothes, races, tribes, socioeconomic strata, diet and climate. Though the incidence of allergic disorders is rising alarmingly, the number of studies done is not adequate. In view of limited data as well as studies pertaining to Allergic testing in Indian subcontinent, it is important to understand and review the various factors which may help the Clinicians decide the timely future course of action. In our retrospective study, we reviewed the positivity of specific IgE allergens in Indian Population. We have majorly focused on the allergen groups and how this information can be used to address health concerns in adults and children. Comparison between total and specific IgE was analysed along with quantification of IgE antibodies in the diagnosis of allergic patients. It is necessary to make this comparative assessment for better understanding of impact of allergies. Identifying the causative allergen can help in early diagnosis and management of the disease.

Materials and Methods

This retrospective study was conducted at Global Reference Laboratory, Mumbai, Maharashtra, India, from May 2020 to May 2022 from the data available in Laboratory Information System (LIS) of the laboratory.

The approval was obtained to use this Laboratory Information Management System (LIMS) data for publication from Independent Ethics Committee.

Results

Discussion

Allergic disorders have been showing an increasing trend in the world. The upsurge in allergies is observed as societies become more affluent and urbanized. It is not easy to distinguish which allergen is causing the clinical symptoms. A test should be able to identify the allergic condition along with disease causing allergen. Symptoms are not just dependent on IgE but also on plethora of factors. Currently there is no gold standard for clinical diagnosis of allergic reactions. Barring a few allergy specialists who still are dependent on skin prick tests, most of the physicians use screening tests like Total IgE, ImmunoCAP Phadiatop screening and specific IgE tests against allergens, along with symptoms for clinical decisions.^[11]

In our study, among those tested for specific allergens, overall, 30% were positive for allergies. In a similar study done on Jordanian cohort by Khasawneh R et al., prevalence of 20% was reported.^[6] This was in agreement with another study conducted in South India by Nitin Joseph et al. where 28.7% of the participants reported having allergies.^[12] Another Indian Study by Prasad R et al claimed that 20% to 30% of the population suffered from allergic disorders.^[1] Contrary to above mentioned studies, a Swedish study done by Enroth et al. has reported 42.3% positivity of allergy based on self-reporting by patients.^[12], ^[13] Similarly, self-reporting by patients has shown an increase of 41.7% allergies in an American study by Seite S et al.^[14]

In our study, the allergy testing was found to be slightly higher in women (52.88%) as compared to men (47.11%). As per an American study by National Health and Nutrition Examination (NHANES) women tend to self-document poor health and notice symptoms earlier than men.^[14] As per study done in Vienna by Erika Jenson et al., women are more prone to develop allergies due to hormonal interactions. (18). Another study by Eva Untersmayr et al. also mentions that female sexual hormones elevate the risk for allergy. ^[15]

39.94% patients had at least one allergen positive while 3.63% patients were positive for two allergens in our study. This was in accordance with an American study by National Health and Nutrition Examination (NHANES) where 44.6% of patients had at least 1 allergen positive.^[14] This describes the demographic distribution of allergic disorders and proves burden of allergic disorders is not lesser.

In our retrospective study, the positive rate of Total IgE among all age groups was 74.66%. The positive rate of Total IgE with Specific IgE was found to be between 75-95.9%, while 4-13.66% was found to be negative for Total IgE but positive for Specific IgE. As per study done in China by Man-Li Chang, 65% patients showed an increase in Total IgE. However positive correlation between IgE and Specific IgE was only 29% in their study contrary to our results.^[16] Probable reason for this, is allergic disease being more probable when Specific IgE is high. However, increase in Total IgE is not specific for allergy and can be high in parasitic infections, multiple myeloma, liver disease and rheumatoid arthritis as well.^[16]

To understand whether specific IgE is better than Total IgE or vice versa, we evaluated the usefulness of total serum IgE and allergen specific IgE. In our study, 40-60% of patients with normal IgE were negative for allergy which is in agreement with the study done by Rame Khasawneh et al. in Jordan which emphasized 44% of cases with normal Total IgE do not indicate absence of allergy and 20% of cases with high level of Total IgE do not indicate an allergy.^[6] The probability of allergic reaction is high when the level of Specific IgE is high as the specific B cells are induced when allergens enter the body. Therefore, increased Specific IgE lead to increase in Total Ige. However, the level of specific IgE should be high enough to have a direct impact on Total IgE.^[16]

Our study showed prevalence of dust allergy was 62.18%, insect allergen was 52.69%, and food allergy was 51.78%. House dust mite (58.90%) was seen to be most common. Among the insect allergy group, mosquito had the highest positive rate of 60% followed by Cockroach (52.58%). Incidence of food allergy was highest in the 0-3 year’s age group. Amongst these, egg yolk allergies were highest (26.95%) followed by cow milk (25.51%). Food allergens such as Plaice fish (31.25%) and Pecan nut caused the highest allergy amongst 7-12 years age group. Dust and insect allergens are common in patients affected by Allergic Rhinitis and are the main causes of Allergic Rhinitis and Allergic Asthma.^[7], ^[17] In India alone, 20 to 30% of the population suffer from Allergic Rhinitis while global prevalence is around 15 to 30%.^[17] Allergic disorders may be high owing to the diverse geographical area and seasonal variation.^[17] Also smoking, drinking habits, pets and family history were common in Asian countries while focus is more on effects of pollens, drugs pets, and family history in western countries.^[18]

Most common allergens reported were comparable to a study by Kammili Jyothirmayi et al. from Bengaluru, South India which reported highest prevalence of dust mite (32.48%) followed by pollens (27.48%).^[17] This was coherent with a Jordanian study by Rame Khasawneh et al. who reported total house dust mite allergy as 24.2% (13.6% - dermatophagoides pteronyssinus, 10.6% - dermatophagoides farina) followed by grass mix and pollens 20.3% (grass mix- 12.8%, grass pollen- 7.5%) and cat 10.6%.^[6]

Asthma symptoms were more prevalent in developed countries. Some areas in Africa and the Indian Subcontinent had the lowest prevalence. This may be due to genetic factors and changing environmental exposure in Asia & Africa.^[19]

As per our study, Cow’s milk allergy was 25.5% until 3 years of age which reduces to 15.5% by the sixth year of life. This bores resemblance to a study conducted in New York, USA by Sampson HA et al. who states that Cow’s milk allergy affects 2.5% newborns in the first year of life who outgrow them by the third year.^[20] This is also supported by a pediatric Japanese study by Uriso et al. which states that the number of patients decreases with increase in age for common causative food items like eggs, wheat, dairy products, buckwheat, shrimp and peanuts.^[21] A slower maturation of the immune response that normally occurs during the initial 12 to 18 months of life is what predisposes a child to the subsequent development of allergy and asthma.^[21] Some epidemiological studies have shown a link between hygiene hypothesis and Immune response while in some studies there is no link.^[22]

As physical, biochemical and immunological barriers are underdeveloped during the initial period of life, allergy to food is very common in pediatric age group. Currently management of allergy involves avoidance of the causative allergen and therapeutic remedy in case of unintended contact or ingestion. As allergy is a lifelong chronic condition, avoidance can be challenging and sometimes it is difficult to identify the allergen. Coping with allergy symptoms create a burden in day-to-day life contributing to poorer quality of life.^[14]

Limitations

Clinical condition and treatment history for allergic symptoms was not available.

False positive results may occur in low positive IgE results (0.35 kUA/L– 3.00 kUA/L) due to cross-reactive carbohydrate determinant (CCD) interference in assays. Using a non cellulose based assay or a (CCD) inhibitor can alleviate CCD-IgE interference.^[23]

Conclusion

The growing prevalence of allergy and asthma in India has become a major health concern with symptoms ranging from mild rhinitis to severe asthma and even life-threatening anaphylaxis. We found that house dust mite allergen has been recorded to have the highest prevalence in Indian population followed by food and insect allergies. Total IgE and specific IgE can never replace each other, however combining the two tests together along with clinical manifestations will improve the interpretation. The positive correlation between IgE and specific IgE was found to around 95% in our study however 13% were negative for Total IgE but positive for specific IgE. Hence, it is proposed to test for clinically appropriate allergen specific IgE tests, regardless of Total IgE concentration in patients with a history of an acute allergic reaction to know the cause of allergy. The availability of multiple and allergen specific panels has proved to be a major tool for the detection and diagnosis of multiple allergies. Detection of allergy is necessary to avoid wrong diagnosis and mismanagement of disease. It is necessary to increase awareness and educate our healthcare workers and patients regarding allergy testing to propagate information to patients and caregivers. Partnering with regional, national, and international allergy societies may help to flatten the allergy epidemic curve.

Source of Funding

None.

Conflict of Interest

None.