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 Table of Contents  
ORIGINAL ARTICLE
Year : 2020  |  Volume : 6  |  Issue : 1  |  Page : 28-33

Autologous serum skin test as an indicator of chronic urticaria in comparison with serum IgE level at a tertiary care center in North-Eastern India


Department of Dermatology, Mata Gujri Memorial Medical College and LSK Hospital, Kishanganj, Bihar, India

Date of Submission21-Mar-2020
Date of Decision16-Apr-2020
Date of Acceptance27-Apr-2020
Date of Web Publication20-Jul-2020

Correspondence Address:
Deblina Bhunia
Department of Dermatology, Mata Gujri Memorial Medical College and LSK Hospital, Purabpali, Dinajpur Road, Kishanganj - 855 108, Bihar
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jcrsm.jcrsm_19_20

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  Abstract 


Introduction: Chronic urticaria (CU) is as a distressing condition that may present with short-lived itchy weal, angioedema, or both. Autologous serum skin test (ASST) is a simple in vivo clinical test for the detection of basophil histamine-releasing activity. ASST is a very simple, quick test which consists of intradermal injection of patient's own serum into the volar aspect of forearm. A significant association between increased total IgE and CU severity was found. The present study was done to find out the clinical profiles of CU in MGM Medical College and LSK Hospital. ASST was done, and serum IgE level in patients with chronic spontaneous urticaria estimated and to give an insight on degree of serum IgE level with ASST positivity.
Materials and Methods: This was a cross-sectional study where a total of 100 patients were enrolled. Detailed history, physical examination, and routine investigations were recorded for all patients. ASST and serum IgE were done in all patients.
Results: Of total of 100 patients enrolled in the study, ASST positive group consists of 29 patients and ASST negative group consists of 71 patients. A total of 46 patients got raised IgE, and the rest 54 had normal IgE level; out of IgE positive, 34 patients were ASST negative, and rest 12 patients were ASST positive. Majority of ASST positive patients had normal serum IgE level (n = 17). Nine and three patient's IgE level were in the range of 200–300 and 300–400 IU/ml, respectively.
Conclusion: The ASST is a simple, practicable in vivo intradermal test for the detection of autoimmune urticaria. There was significant association seen with the duration of disease and ASST positivity. The present study did not show any association between increased serum IgE and ASST positivity.

Keywords: Autologous serum skin test, chronic urticaria, IgE


How to cite this article:
Saha PK, Ranjan R, Kundu S, Bhunia D, Datta PK. Autologous serum skin test as an indicator of chronic urticaria in comparison with serum IgE level at a tertiary care center in North-Eastern India. J Curr Res Sci Med 2020;6:28-33

How to cite this URL:
Saha PK, Ranjan R, Kundu S, Bhunia D, Datta PK. Autologous serum skin test as an indicator of chronic urticaria in comparison with serum IgE level at a tertiary care center in North-Eastern India. J Curr Res Sci Med [serial online] 2020 [cited 2020 Aug 7];6:28-33. Available from: http://www.jcrsmed.org/text.asp?2020/6/1/28/290244




  Introduction Top


The term “urticaria” means a condition that may present with short-lived itchy wheals, angioedema or both. It may be spontaneous or inducible. Individual hives can last as briefly as 30 min to as long as 36 h. They can be as small as a millimeter or 6–8 inches in diameter (giant urticaria).[1] Urticaria may be classified on the basis of underlying etiology or by a clinical classification. In most cases of chronic urticaria (CU), it will not be possible to identify the underlying cause, i.e., the rash is idiopathic; however, when seeing a patient, it is helpful to use a clinical classification, as this guides history taking and ensures that in any one individual all possible triggers for the urticaria are identified. CU is defined by the recurrent episodes occurring at least twice a week for 6 weeks.[2] In 1983, Leznoff et al.[3] suggested an autoimmune basis for the urticaria. In 1988, Gruber et al.[4] detected functional anti-IgE antibodies and proposed that these could be the cause of urticarial wheals.[5]

Most cases of CU are considered idiopathic. It has recently been accepted that autoimmunity plays a critical role in its pathogenesis in some of these patients. CU is associated with diverse clinical presentations. It is chiefly characterized by the rapid appearance of wheals and/or angioedema. A wheal consists of three typical features: (i) a central swelling of variable size; (ii) an associated itching or sometimes burning; and (iii) a fleeting duration of usually 1–24 h.[6] Females are more commonly affected than males.[7] Angioedema is a descriptive term for deep swellings of the dermis, subcutaneous, or submucosal tissues. They are usually painful, rather than itchy.

Point prevalence between 0.5% and 1.0% for chronic spontaneous urticaria has been proposed but a lower figure of 0.11%–0.14% for acute and chronic urticarial.[1] Urticaria may occur at any age. Acute spontaneous urticaria often presents in the childhood, but the peak incidence of chronic spontaneous urticaria is in the fourth to fifth decades. Women outnumber men by 2:1 with chronic spontaneous urticaria, but there is no consistent sex difference in either acute spontaneous urticaria or the inducible urticarias.[8]

The degree of serum IgE increases with the severity of chronic spontaneous urticaria. IgE level usually more than 175 U/ml in severe chronic spontaneous urticaria as compared with the mild and moderate form of urticaria.[9] Autologous serum skin test (ASST) is a simple in vivo clinical test for the detection of basophil histamine-releasing activity. Sabroe et al.[10] found that ASST has a sensitivity of approximately 70% and a specificity of 80%. ASST is a nonspecific screening test that evaluates the presence of serum histamine-releasing factors of any type, not just histamine-releasing autoantibodies. It is a very simple, quick test which consists of intradermal injection of patient's own serum with a 0.4-mm needle into the volar aspect of forearm. The reading is taken 30 min later, and the diameter of the wheal at the test site is measured. Positive reading means diameter at the test site should be at least 1.5 mm larger than the negative control.[11],[12],[13]

There are several studies which have shown that there is the direct relation between the elevated serum level of IgE and the CU.[14],[15] The present study was done to find out the clinical profiles of CU in MGM Medical College and LSK Hospital; and to do ASST and estimate serum IgE level in patients with chronic spontaneous urticaria and to give an insight on degree of serum IgE level with ASST positivity.

Aims and objectives

  1. To know the clinical profiles of CU
  2. To know the ASST positivity in patient with CU
  3. To compare ASST positivity with the degree of serum IgE positivity.



  Materials and Methods Top


Patients attending in the Dermatology Outpatient Department (OPD) of MGM Medical College and LSK Hospital Kishanganj, Bihar, with clinically confirmed CU were taken for study. Altogether 100 patients of CU were recruited with the following inclusion and exclusion criteria: all morphological variants of CU patients with or without angioedema, pretreated or untreated were included. Patients with acute urticaria, acute intermittent urticaria, angioedema without urticaria, CU which had been treated with systemic or topical corticosteroid, immunosuppressants or systemic and topical anti-inflammatory agents within last 1 month; and finally, urticaria associated with some skin diseases such as bullous pemphigoid or underlying systemic diseases were excluded from the study.

After taking informed written consent, a detailed history of the sign and symptoms and duration of the disease was taken. Dermographism study was done for each and every patient. A detailed history was taken to rule out any physical or inducible urticaria. Furthermore, history of taking antihistaminic, nonsteroidal anti-inflammatory drugs, and steroid within the 3 days prior was taken. Family history of atopy, family history of chronic spontaneous urticaria within the family, especially in the first-degree relationship was taken. Blood samples were sent for the following investigations such as complete blood count, thyroid profile, fasting blood sugar, postprandial blood sugar, and serum IgE.

Venous blood was collected into sterile red-topped plastic tubes without accelerator or anticoagulant. Blood was allowed to clot at room temperature for 30 min before the separation. After 30 min, the tubes were put in the centrifuge machine for 10 min with rpm of 2000. Immediately after the forearm of the patient was cleaned with surgical spirit and dried. Then, three insulin syringes were taken one each for the histamine, serum, and normal saline (NS). Five unit of insulin syringe of each was loaded and injected over the volar aspect of the forearm, having distance of 4 cm in between each injection site. Each injection site was labeled with a pen. Then, the patient was asked to wait and do not apply anything on the forearm. The readings were checked after 1 h for the erythema, wheals, and flare. The histamine used was the histamine diphosphate 10 μg/ml.



ASST is positive if ASST mean wheal – NS mean wheal ≥1.5 mm.[13],[14]


  Results Top


A total of 100 patients of CU were taken and about (n = 64) 64% were female and (n = 36) 36% were male. The age-wise incidence was most in the 21–30 age group (39%) of total patients, in which 21 were female (53.84%) and 18 were male (46.15%). Mean age of patients was 33.56 ± 2.82. The group which was on the second most commonly affected was the age 31–40 (26%) of total patients of which female predominated with the (n = 22, 86.61%) and males only (n = 4, 15.38%). We did not get any patients of urticaria in 0–10 years' age group. The age group containing the minimum patients was above 40 years. The incidence of the chronic spontaneous urticaria was mostly seen in the females of the age group between 20 and 40 years (43%). The incidence of the chronic spontaneous urticaria in males was mostly common in the age group of 20–30 years (18%), and the second most common in the 30–40 years of age group (4%). The maximum number of patients of ASST positive (n = 12) was seen in the age group of 20–29 years [Table 1]. Minimum number of ASST-positive patients (n = 2) was seen in the age group of 10–19 years. There was no significant (P ≤ 0.005) relation to asst positivity and age of the patient [Table 2].
Table 1: The autologous serum skin test results in relation to age (n=100)

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Table 2: The autologous serum skin test results in relation to the duration of disease (n=100)

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Majority of the ASST-positive patients 12% (n = 12) were seen in the duration between 13 and 24 months of onset of disease (urticaria), which was significant (P = 0.005) [Table 2]. Among the 100 patients of CU, only 9% of patients had given association with the history of atopy in their childhood or later in the age. Out of which, more than 50% were female. Family history of CU was not common among the ASST-negative patient but up to 4%, it was seen in the severely affected ASST positive patient. TSH was increased in 5% of total patient. Out of total 5% of increased TSH, 3% were ASST negative and 2% were ASST positive [Figure 1]. Among the 100 patients taken total ASST positive patient were total 29 (29%) (males = 9, females = 20) and negative were 71 (71%). Mean age for ASST positive in female patients was 33 years, and for male, it was 29 years.
Figure 1: A positive autologous serum skin test: Significant wheal and flare response seen at serum (AS) and histamine (h) injection sites only. The serum-induced wheal has both redness score = 2 (compared with histamine-induced redness) and a diameter ≥1.5 mm than the saline (normal saline) induced wheal at 30 min

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Out of total 100 chronic idiopathic urticaria patients, 54 (54%) had normal serum IgE level. Forty-six patients (46%) had abnormal serum IgE, in which maximum number of patients (n = 24) had serum IgE level between 201 and 300 IU/ml [Table 3] and [Table 4].
Table 3: Relation between serum IgE and autologous serum skin test positivity (n=100)

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Table 4: Serum IgE level among chronic urticaria (n=100)

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Majority of ASST positive patients had normal serum IgE level (n = 17). Nine and three patients were in the range of 200–300 and 300–400 IU/ml, respectively [Table 5].
Table 5: Level of serum IgE with autologous serum skin test positivity (n=100)

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  Discussion Top


The present study was conducted in the Department of Dermatology, Venereology and Leprology, MGM Medical College and LSK Hospital, Kishanganj, Bihar, India. It included 100 cases of CU who presented in skin OPD. A total of 100 patients of CU were taken, and about 64% were female and 36% were male. It was similar to the study done by Amee et al.[15] The mean age of the patients in this study was 33.56 ± standard deviation 12.82. The incidence was the highest in the 21–30 years' age group (39%), of which 21% were female and 18% were male. The group which was second most commonly affected was the age group of 31–40 years (26%), of which female predominated with the 22% and males were only 4%. The female predominance of this study was similar to Vikramkumar et al.'s[16] study and several other studies like Amee et al.[15] Up to the age of 40 years, percentage of ASST positivity was similar to a study done by Vikramkumar et al.[16] After 40 years, the present study showed more incidence of ASST positivity than their study. The age group containing the minimum number of patients was above 40 years. The incidence decreased with the increase in the age.[16]

The disease was more common in the females, the 20–40 age group showed the maximum 43% of patients. Incidence of the chronic spontaneous urticaria in males was mostly common in age group 20–30 years (18%) and second most common was in the 30–40 years of age group (4%). Median duration of the disease was 24 months and 12 months in ASST positive and ASST-negative groups respectively. It was statistically significant (0.004) which is similar to study done by Inamadar and Palit.[17] But following studies done by Al-Hamamy et al.[18] and Greaves[19] did not show any significance with duration of disease. In present study 29 patients were ASST positive and 71 were ASST negative, which is similar to the 26.7% positive in an Indian study done by Godse.[20] In the study by Vohra et al.[21] 35–50% patients were ASST positive, which is slightly more than present study. The following studies showed slightly increased incidence of ASST positivity, like Grattan[22] and O'Donnell et al.[14]

Among ASST positive patients, positive females were 20 and positive males were 9, which corresponds to 68% female and 32% male respectively. This correlates with the study done by Konstantinou et al.[23] and Pokhrel et al.[24] in which the female:male was 76:35, but this was not similar to study done by Vikramkumar et al.[16] M: F (41.6%:58.3%). In this study serum IgE was elevated among CU patients in 45% of cases. Among which 12 were ASST positive and rest 33 were ASST negative. Mohammad Omidian et al.[9] showed 57% (33/55) of patients with raised serum IgE, which is slightly more than the result of present study.

The mean duration of the disease in present study was 21.27 months. Kessel et al.[25] study showed that about 43% of the CU patients had elevated serum IgE similar to my result of 45% of elevated serum IgE. Vohra et al.[21] IgE was detected in not more than 30–40% of ASST-positive patients; this result also was somewhat near to what I got in this study. In present study majority of ASST positive patients had normal serum IgE level (n = 17). Nine and three patients were in range of 200–300 and 300–400 IU/ml respectively i.e., about 41%.

Studies have shown that there was increase in eosinophil count in acute urticaria.[26] However, a lack of peripheral blood eosinophilia and a total absence of eosinophils in patients with CU have also been reported.[27] But we did not find any direct relation of eosinophil count [Table 6] and chronic idiopathic urticaria (ASST positive) neither any conclusive association with increase in the serum IgE level, which was same in the study done by Chang et al.[28] The limitation we had in finding the significance of eosinophil count is that we did not take any control. It would have been better if eosinophil count should have been taken in nonurticaria patients.
Table 6: Eosinophil level in chronic urticaria

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On comparison with the thyroid profile of CU patients it was increased in up to 5% of total cases taken but it did not show any significance association with severity and ASST positivity. Three cases of increased TSH value were seen with ASST positive patients and the 2 were ASST negative, hence it was not conclusive. There was no association seen with vitiligo and diabetes mellitus with chronic spontaneous urticaria. Asero et al.[29] showed that there is association of type 1 diabetes with the CU and Sabroe[10] showed association with diabetes, vitiligo but there was no such association seen in my study, which was similar to the Pokhrel et al.[30]

There was no association seen with vitiligo and diabetes mellitus with chronic spontaneous urticaria. Asero et al.[29] showed that there is association of type 1 diabetes with the CU and Sabroe et al.[31] showed association with diabetes, vitiligo but there was no such association seen in my study, which was similar to the Pokhrel et al.[30]Family history of CU was not common among the ASST negative patients, but up to 4% was seen in severely affected ASST positive patients. Three out of 4 cases were ASST positive, i.e., 3 cases out of 29 ASST positive cases which are approximately 10%. Similar finding was seen in Asero study.[32] It shows that there can be genetic association, but as the number of patients are less hence it will be inappropriate to comment. Also, there was no control group to signify this. In Patel study et al.,[15] family history was present in 1 (3.6%) patient; ASST was positive in 12 (42.9%) patients, which can be correlated with this study. Among the 100 patients of CU, only 9% of patients had given association with the history of atopy in their childhood or later in the age. Out of which more than 50% were females (5 females and 4 males). Regarding atopy, there was no significant difference between serum-positive and serum-negative groups. This was consistent with other studies.[13],[16],[33] The present study was done on the Indian population; hence, flare and erythema were difficult to observe due to dark skin of patients. Hence, the reactivity was mainly decided on the size of wheal formation.

Positive control and negative control were taken to rule out any false result because no wheal with histamine indicates something is not proper, and similarly, wheal with NS would indicate the same, then, test serum result should not be considered. It might be false negative and false positive, respectively.


  Conclusion Top


CU most commonly affects the young adults rather than the extremes of the age group. Females are commonly affected than males, that also in younger age group. No significant association with thyroid disorder, diabetes, vitiligo, and atopy with ASST positivity is found in the present study. This is to be confirmed by further study increasing the sample size. The ASST is a simple, practicable in vivo intradermal test for the detection of autoimmune urticaria. Although basophil histamine release assay is the gold standard for detecting functional autoantibodies, the procedure is lengthy, requires fresh basophils from healthy donors and skilled. There is a significant association seen with the duration of disease and ASST positivity. The present study does not show association between increased serum IgE and ASST positivity. Furthermore, there is no association between the degrees of increase in IgE with ASST positivity.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]



 

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