|Year : 2020 | Volume
| Issue : 4 | Page : 218-223
Evaluation of chronic idiopathic urticaria patients with autologous serum skin test
Avvaru Surekha1, Prakash Sajja2, K Sridevi3, G Ramesh Kumar3, T Ram Sharan1
1 Department of Dermatology, Venereology and Leprosy, Sri Venkateswara Institute of Medical Sciences, Tirupati, Andhra Pradesh, India
2 Sajja's Skin Clinic, Tirupati, Andhra Pradesh; Department of Dermatology, Venereology and Leprosy, Fathima Institute of Medical Sciences, Kadapa, India
3 Department of Dermatology, Venereology and Leprosy, Sri Venkateswara Medical College, Tirupati, Andhra Pradesh, India
|Date of Submission||22-May-2020|
|Date of Acceptance||05-Jun-2020|
|Date of Web Publication||5-Jan-2021|
Assistant Professor, Department of Dermatology, Venereology and Leprosy, Sri Venkateswara Institute of Medical Sciences, Tirupati 517 507, Andhra Pradesh
Source of Support: None, Conflict of Interest: None
Background: Chronic idiopathic urticaria (CIU) is a common disabling disorder. Sparse published data are available on the utility of autologous serum skin test (ASST) in patients with CIU from south India.
Methods: We prospectively studied 81 patients with CIU and report their demographic characteristics, clinical spectrum and proportion of patients with positive ASST.
Results: Their mean age was 35.2 ± 12.4 years; there were 50 (62%) females. ASST was positive in 39 (48%) patients.Daily attacks of urticaria were seen in 50 (62%), atopy was present in 18 (22%) and angioedema was present in 14 (17%) patients. Their median [interquartile range (IQR)] duration of disease was 28 (6-34) months and median (IQR) duration of single wheal was 20 (10-90) minutes.On univariate analysis, longer duration of single wheal, higher frequency of attacks and presence of angioedema were found to be associate with a positive ASST.
Conclusions: ASST was positive in 39 (48%) patients with CIU. ASST-positive individuals are younger, had a statistically significant longer duration of single wheal (P = 0.001), higher frequency of attacks (P = 0.039) and occurrence of angioedema (P = 0.018). ASST positive patients had severe form of the disease.
Keywords: Autologous serum skin test, chronic, diagnosis, idiopathic, urticaria
|How to cite this article:|
Surekha A, Sajja P, Sridevi K, Kumar G R, Sharan T R. Evaluation of chronic idiopathic urticaria patients with autologous serum skin test. J Clin Sci Res 2020;9:218-23
|How to cite this URL:|
Surekha A, Sajja P, Sridevi K, Kumar G R, Sharan T R. Evaluation of chronic idiopathic urticaria patients with autologous serum skin test. J Clin Sci Res [serial online] 2020 [cited 2021 Jan 20];9:218-23. Available from: https://www.jcsr.co.in/text.asp?2020/9/4/218/306194
| Introduction|| |
Urticaria is a common problem. 15%–20% of the population will have urticaria at least once during their lifetime. The point prevalence of urticaria is 0.1%. Chronic idiopathic urticaria (CIU) is defined as widespread short-lived (<24 h) wheals occurring daily or almost daily for at least 6 weeks, where a physical cause has been excluded. An overall average lifelong prevalence of chronic urticaria is 1%–2%. Studies have shown that the degree of personal, occupational and social disability in patients with CIU is comparable that observed in patients who have triple-vessel coronary artery disease and who are awaiting bypass surgery. CIU is extremely disabling in its severe form and can be difficult to treat.
Mast cell degranulation in the dermis of the skin plays a central role in the development of urticaria. Various identified and unidentified factors are responsible for this mast cell degranulation. Autoimmunity is one of the proposed pathogenic mechanisms for the development of CIU. Two candidate autoantibodies have been identified in patients with CIU. These autoantibodies are immunoglobulin G (IgG) directed against the alpha subunit of IgE receptor (anti-FcεR1α) and IgG directed against the Fc region of IgE (anti-IgE).
Anti-FcεR1α or anti-IgE autoantibodies are present in 30%–50% of patients with CIU. This subset of patients with CIU can be labelled as autoimmune urticaria based on the facts that, the demonstration of reproducibility of positive skin test by passive transfer of serum of patients with CIU in to the skin of healthy individuals, correlation of functional autoantibody levels with disease severity, disease remission following removal of antibodies, strong association of these patients with certain human leucocyte antigen subtypes and association with autoimmune thyroid disease.
Various methods both in vitro and in vivo have been proposed for the identification of this subset of patients with CIU with autoantibodies. Immunoassays such as Western blot analysis or enzyme-linked immunosorbent assay test can be used to detect these autoantibodies. However, some of these autoantibodies are nonfunctional, which makes these immunoassays unreliable for the identification of functional autoantibodies. Most useful method for the identification of these functional autoantibodies is basophil histamine release assay (BHRA). This test utilises the principle of demonstration of release of histamine by the autoantibodies in the serum of patients with CIU when incubated with normal basophils. However, BHRA is expensive, technically demanding, not easily available, requires donor basophils and variability in the histamine release capacity of donor basophils may lead to variability in test result.
Alternative in vivo test is autologous serum skin test (ASST). The induction of a wheal and flare response by the intradermal injection of autologous serum in patients with CIU provides the basis of the ASST. When compared with BHRA at best, ASST has 80% of sensitivity and specificity to identify functional autoantibodies. Moreover, the advantages of ASST over BHRA are ASST is cheap, easily available, quick, not technically demanding and can be performed by a dermatologist.
The ability of ASST to identify a subset of patients with different demographic, clinical features, severity of the disease and response to treatment has been variously reported. Sparse published data are available on proportion of patients with positive ASST and its ability to identify a subset of population with CIU from South India. Hence, the present study was conducted.
| Material and Methods|| |
Consecutive adult patients presenting with CIU to outpatient services of Department of Dermatology, Venereology and Leprosy at Sri Venkateswara Ramnarayan Ruia Government General Hospital (SVRRGGH), Tirupati, a teaching medical college hospital in Andhra Pradesh, South India, were screened for inclusion in the study. Patients with acute urticaria, urticarial vasculitis, physical urticaria, pregnant woman, lactating mothers and patients who are not willing to participate in the study were excluded.
The study was conducted after obtaining clearance from the Institutional Ethics Committee. Written informed consent was obtained from all the study participants. A detailed history regarding duration of disease in months, duration of wheals in minutes, frequency of attacks per day, week and month, presence of atopy, occurrence of angioedema and systemic symptoms including headache, fatigue, pain or swelling of joints, wheezing, flushing, gastrointestinal symptoms and palpitations was obtained. A thorough physical examination was carried out in all the study participants. In all patients, the laboratory investigations carried out were complete haemogram and erythrocyte sedimentation rate.
CIU was diagnosed by the presence of characteristic skin lesions of urticaria and/or angioedema, which appears and resolves repeatedly over a period of 6 weeks or longer. A wheal is identified by the presence of three typical features of central swelling of variable size, surrounded by a reflex erythema, with itching or sometimes a burning sensation over the lesion and disappearance of lesion within 24 h. Angioedema was identified by the presence of episodic submucosal or subcutaneous swelling that is usually asymmetric in distribution and affects nondependent parts of the body, such as the lips, cheeks, periorbital areas of the face and extremities, which develops over minutes to hours and resolves gradually over one to 3 days. The lesions are slightly painful rather than pruritic.
In all patients, an ASST was performed after a wash out period of 1 week. 2 mL of venous blood was collected from antecubital vein and allowed to clot at room temperature. Serum was separated by centrifugation at 2000 rpm for 10 min. 0.05 ml of serum and 0.05 ml of 0.9% saline control were injected intradermally 5 cm apart into the volar aspect of the same forearm, with U-40 insulin syringe with 31G needle [Figure 1]. A wheal response was measured after 30 min. The maximum vertical (d1) and horizontal (d2) diameters of the wheals were measured. Then, the average diameter (D) was calculated by the formula: [D = (d1 + d2)/2]. A positive test [Figure 2] was defined as wheal of =1.5 mm average diameter more than the saline control at the end of 30 min; when the wheal was = 1.5 mm, the test was considered negative [Figure 3].
The data were recorded on a predesigned pro forma and managed using Microsoft Excel worksheet (Microsoft Corp., Redmond, WA). All the entries were double-checked for any possible error. Descriptive statistics for categorical variables were performed by computing the frequencies (percentages) in each category. For the quantitative variables, approximate normality of distribution was assessed. Variables following normal distribution were summarised by mean ± standard deviation; the remaining variables were summarised as median (interquartile range [IQR]). Categorical variables were reported as percentages.
A univariate analysis was carried out to compare the demographic and clinical variables between ASST positive and negative patients using unpaired t-test and Mann-Whitney U-test for continuous variables and Chi-square test and Fisher's exact test for categorical variables. A two-tailed P < 0.05 was considered statistically significant. Multivariable analysis was carried out considering positive ASST as the “dependent variable”, and variables found significant at a P < 0.3 on univariate analysis as predictor variables (covariates), using step-wise binary logistic regression (backward-conditional method). The statistical software IBM SPSS Statistics Version 22 (IBM Corp., Somers NY, USA) was used for statistical analysis.
| Results|| |
One hundred and nine consecutive patients diagnosed to have urticaria were screened for inclusion in the present study. Of these, 28 patients were excluded for reasons being acute urticaria (n = 20), physical urticaria (n = 5) and not willing to participate in the study (n = 3). The remaining 81 patients satisfying inclusion criteria were considered for analysis [Figure 4].
Their mean age was 35.2 ± 12.4 years and there were 50 (62%) females. Angioedema was seen in 14 (17%) patients, atopy was present in 18 (22%) patients and daily attacks of urticaria were present in 50 (62%) patients. Their median (IQR) duration of disease was 28 (6–34) months and the median (IQR) duration of single wheal was 20 (10–90) minutes. Systemic symptoms were seen in 16 (20%) patients. ASST was positive in 39 (48%) patients [Table 1].
On univariate analysis of continuous variables [Table 2], ASST-positive patients had statistically significant longer duration of single wheal (60 [IQR: 10–240] vs. 12.5 [IQR: 5–60]) (P = 0.001) compared to ASST-negative patients. ASST-positive patients had statistically non-significant lower age (32.4 ± 11.5 vs. 37.7 ± 12.8 years) (P = 0.055) and longer duration of the disease (12 [IQR: 3–24] vs. 6 [IQR: 3–24] months) (P = 0.46) compared to ASST-negative patients.
|Table 2: Comparison of demographic and clinical characteristics between patients with positive and negative autologous serum skin test|
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On univariate analysis of categorical variables [Table 2], ASST-positive patients had statistically significant higher frequency of attacks (74% vs. 56%) (P = 0.039) and higher proportion of angioedema (28% vs. 7%) (P = 0.018) compared to ASST-negative patients. ASST-positive patients had statistically nonsignificant higher proportion of female patients (64% vs. 59%) (P = 0.81), higher proportion of personal history of atopy (30% vs. 16%) (P = 0.26) and higher proportion of systemic symptoms (23% vs. 16%) compared to ASST-negative patients. On multivariable analysis, none of the variables emerged as independent predictors of ASST positivity. Comparison of the present study with other studies is shown in [Table 3].,,,,,,
| Discussion|| |
The present study was conceived with the intension to identify proportion of positive ASST and its ability to identify a subset of population among patients with CIU in terms of demographic characteristics, clinical features and severity of disease in a tertiary care teaching hospital.
The mean age (years) of the patients in the present study was 35.2 ± 12.4. Most of the patients belonged to third and fourth decades of life. In the present study, women outnumbered men with a male-to-female ratio of 3:5. These observations are similar to that reported from other studies.,,, In the present study, atopy was seen in 22.5% of patients, which is similar to that reported from other studies., Angioedema was observed in 17% of patients, which is similar to the another study from India. Studies published from Western world reported angioedema ranging from 40% to 80%.,,, Whether this is due to ethnic differences merits further study. Systemic symptoms were observed in 23% of patients, similar to that reported in other study.
In the present study, 48% of patients showed a positive reaction to ASST. Proportion of patients showed positive reaction to ASST ranges from 25% to 50%. ASST positivity in studies from various parts of India ranges from 46% to 50%,,, which is similar to the present study. ASST positivity in studies from other parts of the world range from 24% to 41%,,, which is lower than that reported from Indian studies. As positive ASST is suggestive of presence of circulating vasoactive factors which include autoantibodies. Whether this is due to difference in the aetiology of CIU merits further study.
In the present study, no statistically significant difference in age and sex was observed between ASST positive and negative patients with CIU. Our observations are similar to that reported from other studies,,,,, However, another study showed that the proportion of patients with positive ASST was significantly higher in women than in men. The authors hypothesised that CIU is probably autoimmune in the majority of female patients than male patients. Similar to the observation in other studies,,,, in the present study, there was no statistically significant difference in proportion of patients with atopy and systemic symptoms between ASST positive and negative patients with CIU. Statistically significant difference in proportion of patients with angioedema was noted between ASST positive and negative patients with CIU in the present study. This is similar to that observed in other studies;, however, this was not observed in other studies.,,
In the present study, ASST-positive patients had statistically significant severe disease compared to ASST-negative patients in the form of higher frequency of attacks and longer duration of single wheal. These observations are similar to that reported from other Indian studies.,, Another study from Italy reported similar observations. However, several other studies from Western countries reported no statistically significant difference in the severity of the disease between ASST positive and negative patients with CIU.,, This observation deserves further study to find out relation between high proportion of ASST positivity and association of disease severity with positive ASST in patients with CIU among Indian population.
Further ASST is useful in prognostication and management of the disease. In a study from Germany, ASST-positive patients require significantly more antihistamines and had longer duration of the disease compared to ASST-negative patients with CIU. As ASST positivity indicates the autoimmune nature of the disease in majority of patients and severe disease, this subgroup of patients may benefit from early initiation of other modalities of therapy, such as, cyclosporine, and other immunosuppressive therapies? like plasmapheresis and intravenous immunoglobulins. Observational studies showed that ASST-positive chronic urticaria patients may benefit from plasmapheresis and intravenous immunoglobulins, but randomised controlled trials are required to further clarify this issue. One study demonstrated that the autologous whole blood treatment showed statistically significant reduction in urticarial activity, use of antihistamines and increased quality of life in ASST-positive patients compared to ASST-negative patients with CIU, indicating the therapeutic use of ASST.
Limitations of this study are small sample size, and we did not include histamine positive control due to its unavailability in our setting. Redness of weal and flare reactions is difficult to appreciate in pigmented skin types (e.g., Indian skin).
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Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4]
[Table 1], [Table 2], [Table 3]