Diagnostic accuracy of skin prick test and specific IgE and their association with Total IgE, AEC and serum cortisol in Indian patients with respiratory allergy

Background: Indian subcontinent has high burden of patients suffering from respiratory allergy associated with food sensitization. Immune response is different in skin and blood for allergen sensitization. Skin Prick Test (SPT) and Specifi c IgE (s IgE) allergen positivity is an evidence of sensitization. Both these tests (SPT & sIgE) are often used interchangeably in clinical practice of allergic disorders. In our study the concordance relevance of various tests SPT, sIgE, Total IgE, Absolute Eosinophil Count (AEC) & Serum Cortisol was investigated in 75 patients of respiratory allergy. The aeroallergens were divided into four groups (Dust mite, Pollen, Fungi, Cockroach) & 7 Foods (Milk, Soybean, Wheat, Fish, Peanut, Egg white, Yeast). Total 35 common allergens were tested by SPT. Serum Specifi c IgE estimation was carried out with 16 allergens (D. pteronyssinus, D. farinae, Alternaria alternata, Candida albicans, Aspergillus fumigatus, mesquite (Prosopis julifl ora), common pigweed, goosefoot lamb’s quarter (Chenopodium album), cockroach and seven food allergens (milk, soybean, wheat, fi sh, peanut, egg white, yeast). Methods and fi ndings: A retrospective stratifi ed sample of 75 respiratory allergic patients within age group of 05-70 years was included in the study. Serum total IgE and specifi c IgE levels were estimated by using ImmunoCAP® system and SPT was done by standardized allergens (Allergo Pharma and Greer laboratories Inc.). Following results were compared to evaluate concordance/ discordance between various markers for respiratory allergy. 1. Sensitizations pattern based on Serum (16 specifi c IgE >1 kU/ml) with Skin prick tests Positive >4 mm wheal Size (35 aero-allergens) 2. Serum Total IgE levels >250 IU/ml with Sensitizations based on Serum (16 specifi c IgE >1 kU/ml) with Skin Prick Tests Positive >4 mm wheal Size (35 aeroallergens) 3. Absolute Eosinophil Count >200 cells/uL with Sensitizations based on Serum (16 specifi c IgE >1 kU/ml) with Skin Prick Tests Positive >4 mm wheal Size (35 aero-allergens) 4. Serum cortisol level <10 mcg/dL with Sensitizations based on Serum (16 specifi c IgE >1 kU/ml) with Skin Prick Test Positive >4 mm wheal Size (35 aeroallergens). Research Article Diagnostic accuracy of skin prick test and specifi c IgE and their association with Total IgE, AEC and serum cortisol in Indian patients with respiratory allergy PC Kathuria1*, Manisha Rai2 and Neelam2 1Consultant, BLK Super Specialty Hospital & National Allergy Centre, New Delhi, India 2Clinical Assistant, BLK Super Specialty Hospital & National Allergy Centre, New Delhi, India Received: 23 December, 2019 Accepted: 14 August, 2021 Published: 16 August, 2021 *Corresponding author: PC Kathuria, Consultant, BLK Super Specialty Hospital & National Allergy Centre, New Delhi, India, E-mail:


Introduction
There is a consistent increase in allergic diseases from 10 to 30 % for the last 50 years in India [1]. The global prevalence of Allergic Rhinitis is between 10 to 30 % for adults and as high as 40% for children [2]. SPT and Measurement of sIgE are important tools for diagnosing atopic sensitization and both tests are often used interchangeably. There is no universally acceptable gold standard cut off value for either of these tests associated with allergic diseases, although practice parameter third update guidelines recommends that wheal size threshold of > 3mm cutoff criteria has better clinical accuracy which is based on reproducibility in relation to nasal provocation test.
There are several factors which can modify the test such as skill of the tester, the testing device, the color of the skin, skin reactivity on the day of testing, potency and stability of allergen extract reagent [3,4].
The choice of cut off value for blood specifi c IgE has not been mentioned in guidelines, so Serum specifi c IgE is often overused and misused for allergic diagnosis. The cut off value for sIgE that distinguishes between an allergic and nonallergic individual has been diffi cult to defi ne. Serum specifi c IgE antibody to different allergens have different cut off values depending on the type of the allergens, nature of allergens, concentration of allergen exposure and duration of allergens exposure. Children raised with high exposure to dust mite allergens will have high titers of sIgE antibodies to dust mite allergens [5,6].
There is a strong association between acute episodes of respiratory allergy (Allergic Asthma) with increase in total IgE > 250 IU/Ml). Most individuals have very low level of circulatory serum IgE (<100 IU/ml where 1 IU = 2.4 ng IgE). Allergen specifi c IgE should be considered as a marker for atopy and IgE sensitization but it cannot predict clinical severity of reactions and will have to be interpreted on the basis of the individual's case history [7,8].
There is a complex interaction of neuroendocrine and metabolic immune system. Inhaled corticosteroids are the mainstay treatment for respiratory allergy and there is an increasing concern about their systemic side effects especially adrenal suppression. Basal serum cortisol is an indirect biomarker for detecting suppression of HPAA and the disease severity [9].
Peripheral blood eosinophilia is a hallmark of severe allergic disease and correlates with severity of the disease due to synthesis of IL5-prominent Th2-driven immune response.
Infi ltrating eosinophils release MBP, ECP, and EPO which in turn injure the nasal epithelial cells and induce hyper responsiveness & chronic remodeling [10,11].

Methods
Data from 75 participants coming to outpatient department of National Allergy Centre, presenting with respiratory allergy was analyzed retrospectively. The patients were without history of food allergy as recorded using a standard questionnaire.
All these patients were also sub-categorized into different age groups (Figure 1).
The patients were without any history of food allergy as recorded using a standard questionnaire.
The diagnosis of Respiratory Allergy (allergic asthma with rhinitis) was made based on history and clinical investigations following the criteria of GINA guidelines (2014) [12,13].

Skin Prick Tests (SPT)
Data obtained from SPT tests by various allergens of these patients was recorded. Sensitization to food (7 Allergens) and common environmental allergens (35 standardized):

Statistical analysis
The statistical analysis was performed using SPSS (Statistical Package for Social Sciences) version 10.5 software.
The data was analyzed for all variables using the Chi-square test.  Citation: Kathuria

Total IgE estimation distribution
Total serum IgE estimation was carried out from the available data, cut off range was taken as > 250.0 IU/mL Following distribution was derived from this data   Citation: Kathuria

Discussion on data analysis-Relevance to total IgE, AEC & S. cortisol
In our current study of 75 subjects (n=60, 80%) were poly-sensitized, among which (n=67, 89.33%) (Figure 4) were found to be signifi cant positive with House Dust Mites (D.     Low level of S. Cortisol <10 mcg/dL (N=22, 29.3%) ( Figure   10) was found. Which may be due to the complex interaction of neuro endocrine & immune system or due to exogenous irregular intake of oral corticosteroids [21]. To the best of our knowledge there is no published data attributable to fi nd the signifi cance of lower cortisol level in polysensitized respiratory allergic patients.

Conclusion
Our study has several strengths and limitations that are worth acknowledging. One strength is that our study was based upon data collected from a nationally representative population with a wide range of age. This allowed us to directly compare sensitization rates in subjects of different ages suffering from respiratory allergies (allergic rhinitis bronchial asthma b. Poly-sensitization has strong association with high levels of total IgE>250 IU/ml (n=44, 58.6%) (Figure 9), AEC level cut off >200 cell/uL (n=43; 57.33%) ( Figure 11) and also low level of S. cortisol 10pg/ml (n=38; 50.6%)