Original Article

Efficacy and Safety of Autologous Serum Therapy in Chronic

Spontaneous Urticaria in the Pediatric Population: A Prospective Pilot
Study
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Abstract Akash Agarwal,

Background: Chronic spontaneous urticaria (CSU) in children is mostly spontaneous in Ajaya K. Jena,
onset (57%).Treatment comprises long‑term antihistaminic therapy without need for elaborate Mrutunjay Dash1,
investigations. A subset of such patients don’t respond to conventional treatment and novel therapies
to help reduce pill burden is the need of the hour. Objectives: To determine the efficacy and Maitreyee Panda
safety of autologous serum therapy  (AST) in pediatric patients with chronic spontaneous urticaria. Department of Dermatology,
Materials and Methods: All pediatric patients, aged between 6-16 years, attended to our OPD from IMS and SUM Hospital,
Bhubaneswar, 1Department
March 2019 to March 2020 were recruited. Clinico‑demographic data and baseline investigations of Pediatrics, IMS and SUM
of all patients were performed. Two‑weekly AST therapy was given for 8 visits with levocetrizine Hospital, Bhubaneswar, Odisha,
tablet 5mg on an on‑demand basis. Urticaria activity score (UAS) sheet was provided to record India
and return every 2  weeks. Statistical analysis was done using the IBM SPSS 26 software package.
XMa7Jn4VG4/fUzDlsWE= on 03/16/2023

Results: Autologous serum skin test  (ASST) was positive in 63% patients. Both the ASST positive
and ASST negative group showed significant reduction in UAS7 score at week 14 compared
to baseline. The reduction in mean UAS7 score was associated with a decreased pill burden and
positive response in the patient and physician global assessment scale. No statistically significant
difference between the two groups in terms of mean UAS7 reduction was found. Conclusion: This
study has explored the efficacy and safety of autologous serum therapy in the pediatric CSU patients.
Both ASST positive and ASST negative group respond to AST therapy.

Keywords: ASST, AST therapy, chronic spontaneous urticaria, pediatric patients, pilot study

Introduction plasma extravasation.[3] Treatment includes

Pediatric urticaria has an estimated
incidence of about 3.5%–8%. Acute
urticaria is more common with causes
being viral, food allergy, and rarely drugs.
Chronic urticaria, on the other hand, has
a prevalence close to 1.8%, but the risk
factors are not precisely known. The latter
is defined as occurrence of spontaneous
wheals, angioedema, or both lasting for
more than equal to six weeks. Chronic
urticaria is further divided into two groups:
chronic inducible urticaria  (CIU) and
chronic spontaneous urticaria  (CSU).[1] The
point prevalence of CSU in children ranges
between 0.1 and 0.3%, and it represents
55.9% of pediatric chronic urticaria cases.[2]
The pathogenesis of CSU revolves around
mast‑cell activation. The mediators involved
are histamine, platelet‑activating factor,
leukotrienes, and prostaglandins that induce
sensory nerve activation, vasodilatation, and
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second‑generation H1‑antihistamines as
first‑line therapy.In patients with CSU
not responding to conventional updosing
of second generation H1-antihistaminics,
omalizumab, cyclosporine, first‑generation
H1‑antihistamines, and leukotriene
antagonists, have been tried but no specific
guidelines have been developed in pediatric
population.[4]
Although second‑generation antihistaminics
are considered the first‑line therapy, a Address for correspondence:
recent review concluded that anti‑H1 Prof. Maitreyee Panda,
Department of Dermatology,
anti‑histamine drugs are beneficial in less IMS and SUM Hospital,
than 50% of cases.[1] Therefore, search for Bhubaneswar ‑ 751 013,
a therapeutic modality that can provide Odisha, India.
extended relief and reduce pill burden is E‑mail: pandamaitreyee@gmail.
com
the need of the hour. Autologous serum
therapy containing tolerance‑generating
anti‑idiotype antibodies to mast‑cell Access this article online
degranulating antigens has been tried
Website: www.idoj.in
for disease remission in the treatment of
DOI: 10.4103/idoj.idoj_376_22
How to cite this article: Agarwal A, Jena AK, Quick Response Code:
Dash M, Panda M. Efficacy and safety of autologous
serum therapy in chronic spontaneous urticaria in the
pediatric population: A prospective pilot study. Indian
Dermatol Online J 2023;14:195‑9.
Received: 07-Jul-2022. Revised: 09-Dec-2022.
Accepted: 13-Dec-2022. Published: 03-Mar-2023.

© 2023 Indian Dermatology Online Journal | Published by Wolters Kluwer - Medknow 195
 Agarwal, et al.: AST in pediatric urticaria
chronic urticaria. Many studies have depicted efficacy and
safety of AST in chronic urticaria with almost negligible
side effects.[5] But all these studies included adult
population, and no data is available regarding its safety and
efficacy in children.[6] Our study was aimed to assess the
effectiveness and safety of autologous serum therapy (AST)
gHgjTEP1OL2SXJNvb5ctAFoEFAHdYa2PcbaWgPygH0MO6gU7IJik1WWEZV8GqBJNLl2bLIMwyXkZVlPbOl5AKCwHB55fQsywjgfX
as an adjunctive therapy to standard antihistaminics in
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chronic spontaneous urticaria in pediatric population.
Materials and Methods
The study was a single‑center, prospective pilot study at a
tertiary care hospital in Eastern India. Institutional Ethics
Committee clearance was obtained prior to study initiation,
and written informed consent was taken from patient’s
caregivers. Duration of study was from March 2019 to
March 2020. All pediatric patients  (age between 6 and
16  years) presenting with chronic spontaneous urticaria
XMa7Jn4VG4/fUzDlsWE= on 03/16/2023
were screened for eligibility criteria. Chronic spontaneous
urticaria was defined as itching and wheals occurring daily/
near daily (≥3 times/week) for ≥6 weeks.
Inclusion criteria
• Diagnosed case of chronic spontaneous urticaria (itching
and wheals occurring daily or near daily[> =3 times per
week] for >=6 weeks)
• Age between 6 and 16 years.
Exclusion criteria
• Patient suffering from immunosuppression from drug
and disease
• Hepatitis B, C and HIV infection.
• Inability to come for regular follow‑ups.
• Concurrent infections or thyroid dysfunction.
• Personal or family history of atopy.
• History of physical urticaria or angioedema.
Screening visit
Clinico‑demographic data of all patients were recorded.
Baseline investigations including complete hemogram, liver
function tests, renal function tests, and thyroid panel were
performed. Caregivers were instructed to discontinue oral
antihistaminics and provided urticaria activity score (UAS)
sheet to record and return after 1 week.
Baseline visit
Baseline UAS7 was recorded. UAS was calculated as
wheals  [0: no wheals; 1: <20 wheals/24 hours; 2:  20‑50
wheals/24 hours; 3: >50 wheals/24 hours] and the itch
severity scores  (0: none, 1: mild  (present but not annoying
or troublesome), 2: moderate  (present and annoying but not
interfering with sleep), and 3: severe  (present and interfering
with sleep). Ease of estimation particularly in children was the
reason of preference over use of urticaria total severity score.
Autologous serum skin test  (ASST) was done at baseline
visit. 5  ml venous blood of the patient was drawn with a
196 Indian Dermatology Online Journal | Volume 14 | Issue 2 | March-April 2023
sterile, disposable syringe from the antecubital vein in
sterile BD Vacutainer® (BD, NJ USA) for serum collection.
The blood was subjected to centrifugation using centrifuge
machine  (R‑8C laboratory centrifuge, REMI laboratory
instruments, Mumbai, India) at the rate of 2000  rpm for
10  min at room temperature. 0.05  ml of the serum thus
separated was injected immediately intradermally into the
patients’ left flexor forearm 2 inches below the antecubital
crease and 0.05  ml sterile normal saline as negative
control into right forearm using 31 G sterile disposable
1  ml BD insulin syringe  (BD, NJ USA). The beveled end
of the needle was kept in the upward direction producing
a palpable bleb on the skin. Areas which were involved
by spontaneous wheals within last 48  h were avoided.
A  reading of the weal was taken after 30  min. Patients
having weal of more than 1.5  mm perpendicular diameter
than that of control were considered to be suffering
from autoreactive urticaria  (ASST positive). All patients
irrespective of ASST result were given autologous serum
therapy. 2  ml of the fresh serum separated from the
patients’ blood  (as stated above) was given deep IM into
the upper arm. Patients were asked to take levocetirizine
5  mg tablet on an on‑demand basis but not more than
1 tablet/day. Caregivers were given UAS sheets to record
disease activity on a daily basis. In case of any untoward
side effects, caregivers were instructed to contact the
investigator.
Follow‑up visits
Patients were given AST therapy at an interval of
2  weeks for a total of eight visits including baseline.
UAS7 score was calculated at each visit. UAS7 score
was primary effectiveness parameter. Pill burden using
a score  (0  =  none/week, 1  =  less than once or once/
week, 2  =  2‑3  times/week, 3  =  daily or almost daily/
week) was recorded at each visit. Patient’s Global
Assessment scale  (PGA) and Physician Global Assessment
scale  (PHGA) was calculated at each visit using a 5‑point
Likert scale  (0: no improvement, 1: mild improvement, 2:
moderate improvement, 3: marked improvement, and 4:
excellent improvement). Spontaneously reported adverse
effects were noted at each visit. Baseline investigations
were repeated at end of eighth visit.
Outcome measures
Primary effectiveness outcome: Reduction in mean UAS7
score between baseline and week 14.
Secondary effectiveness outcome: Comparison of
reduction in mean UAS between ASST positive and
ASST negative group. Reduction in pill burden and
comparison with reduction in UAS7 between baseline
and week 14.
Safety outcome parameters: Incidence of spontaneously
reported adverse events and incidence of laboratory
disturbances between baseline and week 14 were recorded.
 Agarwal, et al.: AST in pediatric urticaria

Statistical analysis cognitive impairment during the autologous serum therapy.

Laboratory parameters at the baseline and eighth visit were
The sample size of 29  patients was taken over a duration of
comparable.
1  year. It was a time‑bound study, so we recruited patients
presenting during that duration. Baseline demographic data, Discussion
pill burden, and safety data are presented as mean and standard
gHgjTEP1OL2SXJNvb5ctAFoEFAHdYa2PcbaWgPygH0MO6gU7IJik1WWEZV8GqBJNLl2bLIMwyXkZVlPbOl5AKCwHB55fQsywjgfX

deviation with 95% confidence interval. Urticaria activity A subset of adult and pediatric patients (40%) with chronic
urticaria has a type  IIb autoimmune basis for their disease
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score  (UAS) is presented as mean with standard deviation at

95% confidence interval and median. Modified intention to pathogenesis. It is hypothesized that autoantibodies to
treat analysis was carried out in patients reporting for at least the high‑affinity IgE receptor are responsible for the
one follow‑up visit. Last observation was carried forward to
address the missing data either due to dropouts or patients who
achieved remission. Pre‑  and post‑treatment laboratory values
were compared in patients for whom both sets of data were
available. All data was analyzed using SPSS version 26.

Results
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A total of 29  patients were screened for eligibility criteria,

and five patients were excluded (three did not meet eligibility
criteria and two did not give consent to participate). Two
patients were further lost to follow‑up (failing to report for
at least one follow‑up), and 22 patients were analyzed with
modified intention to treat analysis. Out of 22  patients, 12
were females and 10 were males. The mean age of patients Figure  1: Co‑relation between reduction in mean UAS7 and PGA and
PHGA, PGA: Patient’s Global Assessment scale, PHGA: Physician Global
was 12.09  ±  2.26  years. The mean duration of chronic Assessment scale, 5‑point Likert scale  (0: no improvement, 1: mild
spontaneous urticaria was 6.77  ±  2.02  months. The mean improvement, 2: moderate improvement, 3: marked improvement, 4:
weight was 34.18  ±  5.39 kilograms. ASST positivity was excellent improvement)
seen in 14 out of 22  patients. Both the ASST positive and
negative groups were comparable at baseline [Table 1].
There was statistically significant improvement in the mean
UAS7 at week 14 compared to baseline  (P  <  0.0001).
Significant reduction was noted from the fourth visit after
initiation of therapy. The reduction in mean UAS7 score
correlated positively with the improvement in patient and
physician global assessment scale [Figure 1]. The reduction
in UAS7 was also associated with a simultaneous reduction
in the pill burden [Figure 2].
Reduction in UAS7 between baseline and week 14
was statistically significant in both the ASST positive
and ASST negative groups  (P  =  0.001, ASST positive Figure 2: Comparison between mean UAS7 and pill burden; pill burden,
group) (P = 0.005, ASST negative test) [Figure 3]. However, 0 = none/week, 1 = less than once or once/week, 2 = 2–3 times/week, 3 = daily
or almost daily/week
intergroup comparison revealed no statistically significant
difference between the two groups (P < 0.05) [Table 2].
Injection site pain was the most commonly reported adverse
effect in 50% of patients. None of the parents reported any

Table 1: ASST positive Vs ASST negative group

ASST positive ASST negative P
Mean age (Years) 12.78±1.88 13.12±2.94 0.6537
Gender
Male 8 2 0.145251
Female 6 6
Duration of chronic 6.21±2.15 7.75±1.38 0.085
Figure 3: Mean UAS7 between baseline and week 14 in ASST positive and
urticaria (months) ASST negative groups

Indian Dermatology Online Journal | Volume 14 | Issue 2 | March-April 2023 197

 Agarwal, et al.: AST in pediatric urticaria
Table 2: Table of P value of mean UAS7 between baseline
and week 14 in ASST positive and ASST negative groups
Mean ASST positive ASST negative P patients with ASST positivity, many studies have
UAS7 group group
Baseline 30.42±2.73 29.37±1.92 0.34
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Week 2 29.21±2.72 29.12±2.35 0.9390
Week 4 25.14±2.79 24.37±2.06 0.5071
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Week 6 16.35±5.95 17.37±6.23 0.7084
Week 8 11.07±6.95 14.37±8.39 0.3317
Week 10 7.42±8.42 10.75±9.67 0.4090
Week 12 5.92±9.12 8.5±10.43 0.5526
Week 14 5.14±9.43 7.85±10.06 0.5306
P value 0.0001 0.0005
mast cell and basophil degranulation via cross‑linking of
IgE receptors.[7] This subgroup is termed as autoimmune
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urticaria whose prevalence ranges from 27 to 61%.[6]
There are two methods of detecting these autoantibodies
by either an in vivo test such as the autologous serum skin
test  (ASST) or in vitro test such as the basophil histamine
assay.[8] In children with chronic urticaria, ASST positivity
rates have been found in the range of 35–47%.[9,10] In our
study, a slightly higher incidence of 63% was found.
Children with chronic urticaria suffer from the high
disease morbidity due to the irritable itch and wheals
and are also subjected to a huge antihistamine pill
burden. Several studies reported that, in children with
CU, discomfort caused by itching, aesthetic aspect, and
unpredictability of manifestations can lead to anxiety
and a higher risk of depression. The unpredictability
disease course, high pill burden, and impaired quality of
life associated with CSU in children warrants the need
for adjuvant therapies so as to reduce the morbidity
associated with the disease. Autologous serum therapy
is a promising therapeutic option that has been explored
in the adult population for chronic urticaria. It works on
the principle of induction of anti‑idiotypes to counteract
the autoantibodies in patients with autoimmune urticaria
and also by possibly shifting Th2 response to Th1 type
in patients with ASST positivity.[11] Debberman et al.
and Karn et al. have reported that weekly injections of
intramuscular AST in adult patients with chronic urticaria
show statistically significant improvement compared
to placebo.[6,12] A study comparing intramuscular and
subcutaneous AST therapy in adult chronic urticaria
patients has reported that subcutaneous injection is not
inferior to intramuscular route of administration.[13] In
our pilot, we found encouraging results in the use of
AST in pediatric patients with chronic urticaria. There
was statistically significant improvement in UAS7 score
from the fourth visit onward after initiation of two
weekly AST therapies. The reduction in UAS7 score was
also associated with improvement in both the patient
and physical global assessment score and a significant
reduction in the antihistaminic pill burden.
198
Although, traditionally, the AST therapy was assumed
to have a role only in those subset of chronic urticaria
documented efficacy in ASST negative patients as well.[6,12]
The underlying pathomechanism, however, remains to be
understood. In our study as well, we found that both the
ASST positive and ASST negative groups both responded
to the AST therapy; however, there was no statistically
significant difference between the two groups.
The safety parameters were encouraging with no
deleterious cognitive impairments reported to the therapy
among children in our study. The laboratory parameters
were also comparable compared to baseline. These findings
corroborate to studies in the adult counterpart.[14]
Limitations
There was no control group and there was no followup
after completion of the study period.
Conclusion
In conclusion, two weekly AST therapies represent a
viable option for children with CSU not responding to
conventional antihistaminic up dosing. Apart from being
efficacious in pediatric CSU, autologous serum therapy
helps to reduce pill burden without any deleterious
side‑effects to the child’s development. This study has
explored the efficacy and safety of autologous serum
therapy in the pediatric CSU patients with promising
results. Both ASST positive and ASST negative groups
respond to AST therapy and help reduce pill burden.
A comparative study with a placebo group may be a future
research prospect to confirm findings noted in our study.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
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