Received: 20 June 2023 | Accepted: 19 January 2024

DOI: 10.1111/jdv.19904

SYSTE M ATIC R EV I EW

Treatment of acute urticaria: A systematic review

Fariza M. S. Badloe1,2 | Martine Grosber1 | Johannes Ring3 | Inge Kortekaas Krohn1,2 |

Jan Gutermuth1,2

1
SKIN Research Group, Vrije Univeristeit
Brussel (VUB), Brussels, Belgium Abstract
2
Department of Dermatology, Vrije There are only a few clinical trials which address the treatment of acute urticaria
Universiteit Brussel (VUB), Universitair (AU). Especially, the added value of systemic corticosteroids to antihistamines is un-
Ziekenhuis Brussel (UZ Brussel), Brussels,
Belgium clear in treatment of severe AU. To review the existing evidence-­based approaches
3
Department of Dermatology and Allergology for AU treatment. A systematic electronic search was done in PubMed and Web of
Biederstein, Technical University Munich, Science to retrieve all studies on the treatment of patients with AU. A descriptive
München, Germany synthesis was conducted based on the PRISMA statement. Quality assessment was
Correspondence independently performed by both reviewers (‘Cochrane risk-­of-­bias tool’ for RCTs).
Fariza M. S. Badloe, SKIN Research Ten randomized controlled trials (RCTs) (n = 857 participants) were included. Four
Group, Vrije Univeristeit Brussel (VUB), studies assessed corticosteroid effectiveness added to antihistamines and six studies
Laarbeeklaan 103, Brussels 1090, Belgium.
Email: [email protected] compared the efficacy of H1 and/ or H2-­antihistamines. The addition of corticoster-
oid (prednisone) to an antihistamine (levo)cetirizine did not improve symptoms of
AU compared to antihistamine alone in two out of three RCTs. The combination of
diphenhydramine (50 mg, IV) and ranitidine (50 mg, IV) or cimetidine (300 mg, IV)
was most efficient for relief of urticaria in two out of five studies. Most frequent ad-
verse effects were sedation and drowsiness. Recent guidelines on urticaria treatment
mainly focus on chronic urticaria rather than on AU. Moreover, only few, small RCTs
provide evidence for the management of AU. Thus, the state-­of-­t he-­art management
of this frequent condition remains unclear. The addition of corticosteroids to an
antihistamine as treatment for AU needs to be further investigated. Well-­designed,
high-­quality interventional trials are needed to establish evidence-­based treatment
guidelines for AU.

I N T RODUC T ION Wheals can vary in size with central swelling surrounded by
erythema, they are usually highly pruritic and usually resolve
Spontaneous urticaria is the most common form of urticaria. within 30 min to 24 h. Angioedema is an erythematous or
Approximately 20% of the general population will be affected skin-­coloured swelling as a result of urticaria that occurs in
by spontaneous urticaria at some point in their lives.1,2 Based the lower dermis and subcutis or mucous membranes. Acute
on its duration, spontaneous urticaria can be classified as acute urticaria (AU) develops within several seconds or minutes, and
spontaneous urticaria (≤6 weeks) or chronic spontaneous ur- single lesions resolve without scarring within less than 24 h;
ticaria (>6 weeks). Acute spontaneous urticaria (or acute urti- episodes of AU often resolve within days. AU may reoccur over
caria) is defined as a reaction of the skin, characterized by a weeks and if the progress takes longer than 6 weeks it will be
rapid onset of wheals (hives), angioedema or both.1 The under- reclassified as chronic urticaria.1,3,4
lying pathophysiologic mechanism of urticaria is the release Acute urticaria is one of the most common dermatolog-
of histamine, heparin and multiple other preformed media- ical conditions treated in the emergency department. The
tors from mast cells in the dermis and circulating basophils, underlying cause cannot be identified in about 50% of the
resulting in sensory nerve activation, vasodilation and leak- cases and patients are classified as ‘idiopathic’.5,6 Drugs such
age of fluid and cell recruitment, which results in urticaria.1,3 as NSAIDs (including ibuprofen or aspirin) could be one of
Linked article: E. Kocatürk et al. J Eur Acad Dermatol Venereol 2024;38:2047–2048. https://doi.org/10.1111/jdv.20320.

© 2024 European Academy of Dermatology and Venereology.

2082 | 
wileyonlinelibrary.com/journal/jdv J Eur Acad Dermatol Venereol. 2024;38:2082–2092.
 14683083, 2024, 11, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/jdv.19904 by Bauman Moscow State Technical University, Wiley Online Library on [28/10/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
BADLOE et al.     | 2083

the factors to trigger urticaria.3 AU also can be caused by Information sources

IgE mediated hypersensitivity reactions to food or drugs.1,3
Infections, especially in children, are frequently regarded An electronic search of PubMed® and Web of Science was
as possible trigger factors for urticaria.5,7,8 Viral infections, conducted. The date of the last search was on 26 May 2023.
including Epstein–Barr, Hepatitis (A, B, C), herpes simplex Backward and forward citation searching was performed
and enterovirus, are linked to AU.9 to capture additional studies not included in the database
Diagnostic approaches are based on patient history and search. The search strategy for PubMed was developed and
physical examination. Laboratory testing without clinical adapted to the syntax and subject headings of the other
indication is not recommended.1,4 In general, management databases.
considerations for AU consists of the identification of un-
derlying causes and treatment for symptomatic relief.1,4
Antihistamines are the first line of treatment for all pa- Search strategy
tients with AU. However, there are still some inconsisten-
cies between studies and guidelines on the use of H1 and/ or A search strategy was developed to retrieve all studies re-
H2-­antihistamines and corticosteroids as treatment. Some porting the management of patients with AU from PubMed®
studies and guidelines recommend H2-­antihistamines in and Web of Science. ‘Acute urticaria’ was combined with the
addition to H1-­antihistamines for persistent cases, despite following key words: disease management, guideline, pro-
weak evidence to support its use.4,10,11 A short course of cor- tocol, diagnosis, treatment and therapy. The search strategy
ticosteroids is recommended by recent guidelines for severe included both free text searching and controlled vocabulary
cases of AU.1 However, randomized controlled trials on the searching. Search strategies of the databases are included in
use of corticosteroids are lacking. Tables S1 and S2. To identify RCTs, the Cochrane's highly
The objective of this study is to determine and summa- sensitive search strategy for RCTs in PubMed was used.
rize the evidence-­based approaches of managing AU by
identifying and systematically reviewing all studies on the
management of AU. Treatment of persistent AU cases that is Study records
inherently based on the use of corticosteroids is particularly
challenging, as there is limited evidence to support its use Data management
and there is often conflict between reliable available studies
and accepted AU treatment guidelines. All references were uploaded in a reference manager (Endnote
X9™) followed by removal of duplicates. Rayyan, a software
for systematic reviews13 was used for the selection of studies.
M AT E R I A L S A N D M ET HODS

Reporting of this systematic review was prepared in ac- Selection process

cordance with the PRISMA 2020 guidelines.12 Methods
were predefined in a protocol registered at Prospero Studies were imported from the electronic databases into
(CRD42017077008; https://​w ww.​crd.​york.​ac.​u k/​prosp​ero/​), an Endote X9™ library followed by the automated removal
an international prospective register of systematic reviews. of duplicates. A two-­step process was used to assess the re-
For the present review, only randomized controlled trials sults of the literature search. Two reviewers independently
(RCTs) on the treatment of AU were included. Guidelines screened the titles and abstracts according to the pre-­
and non RCT were excluded. specified criteria to exclude not relevant articles. The articles
selected for inclusion were reviewed in full and indepen-
dently assessed for eligibility. Full text files were found using
Eligibility criteria Endnote X9™ or manually in digital sources when not pro-
vided by Endote X9™. Studies were excluded when full-­text
This systematic review included all available studies report- files were not available. Disagreements at any point during
ing the treatment with AU or hives. RCTs on the treatment the selection process were resolved by consensus or a third
of AU were included. The age range of the study population reviewer. Additional studies were added through backward
was not taken into account. Studies on chronic urticaria, and forward citation searching of the included studies. The
hereditary angioedema, angioedema without urticaria and PRISMA flowchart was used to depict the flow of the study
studies in which urticaria was not specified as acute were selection (Figure 1).
excluded. Commentaries, case series, case reports, abstracts,
posters, conference papers, letters, review articles, editorials,
expert opinions and non-­human studies were excluded dur- Data collection process
ing the screening process. Studies in languages other than
English, Dutch, German or French were also excluded. This For all included studies, data were extracted into a custom-
study imposed no restriction on the date of publication. ized data sheet. Data extraction forms were specifically
 14683083, 2024, 11, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/jdv.19904 by Bauman Moscow State Technical University, Wiley Online Library on [28/10/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
2084 |    TREATMENTS OF ACUTE URTICARIA

Identification of studies via databases and registers

Records identified from:

Identification Databases (n = 2882)
PubMed (n = 1906)
Web Of Sciences (n = 976)

Records removed before screening:

• Duplicate records removed
(n = 630)

Records screened
(n = 2252)
Screening

Records excluded
(n = 2203)

Reports sought for retrieval

(n = 49)

Records not retrieved

(n = 2)
Eligibility

Reports assessed for eligibility

(n = 47)

Reports excluded:
• Wrong outcome (n = 17)
• Wrong publication type (n = 17)
• Wrong study design (n = 3)
Inclusion

Studies included in review

(n = 10)

F I G U R E 1 PRISMA 2020 flow diagram for systematic reviews. Flow diagram of the selection process. Ten studies meeting the inclusion criteria
were included in this systematic review. From: Page et al. (2021).12

developed for the current study. The forms were pilot tested In case of missing data within the included studies, at-
on three random selected included studies. Two independ- tempts were made to contact the authors to collect the
ent reviewers completed the data extraction for all included missing data.
studies. The data items extracted from the studies included:
author, year, country of study, study type, patient group,
sample size, age, gender, duration of study, interventions, Outcomes and prioritization
outcomes and key findings. Any discrepancies were resolved
by discussion or by arbitration by a third reviewer if agree- The primary outcome was to study the effect of the treat-
ment could not be found. ment of AU according to the current guidelines, defined by
relief of urticaria, with relief of pruritus, resolution of rash
(intensity and extent of wheals) and perception of overall im-
Data synthesis provement. The secondary outcome measure was to describe
the adverse effects of the treatment.
A descriptive synthesis was conducted in line with the
PRISMA statement.12 Text and tables were used to sum-
marize and explain the characteristics and the findings of Risk of bias in individual studies
the included studies. A ‘narrative synthesis’ was chosen as
approach for the data analysis. As the majority of research ‘Risk of bias’ or ‘quality assessment’ was performed inde-
addressing AU treatment was descriptive, there was a lack of pendently by two reviewers for all included studies. The
comparable statistical data. Therefore, quantitative synthesis third reviewer mediated in situations of disagreement. For
(e.g. meta-­analysis) was not appropriate. the risk of bias in RCTs, the Cochrane Risk of Bias (RoB) 2
 14683083, 2024, 11, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/jdv.19904 by Bauman Moscow State Technical University, Wiley Online Library on [28/10/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
BADLOE et al.     | 2085

tool was used.14 The overall risk of bias judgement for each every 4–8 h) plus prednisone (20 mg, PO, every for 4 days;
study was stated as ‘high risk of bias’, ‘low risk of bias’ or n = 24) or diphenhydramine (50 mg, IM) in the emer-
‘some concerns’ with a clear descriptive support of the given gency department, followed by hydroxyzine (25 mg, PO,
judgement. every 4–8 h) plus placebo (n = 19). Palungwachira et al.17
compared the combination of intravenous (IV) chlor-
pheniramine (10 mg, IV) in the emergency department,
R E SU LT S followed by cetirizine (10 mg/day, PO for 7 days; n = 25)
versus patients receiving chlorpheniramine plus dexa-
Study selection methasone (5 mg, IV) in the emergency department, fol-
lowed by cetirizine (10 mg/day, PO, for 7 days; n = 25) and
The systematic search identified a total of 2882 articles using a group of patients receiving chlorpheniramine (10 mg,
PubMed (n = 1906) and Web of science (n = 976) (Figure 1). IV) plus dexamethasone (5 mg, IV) in the ER, followed
After removal of duplicates (n = 630), 2252 articles were in- by cetirizine (10 mg/day, PO, for 7 days) plus prednisolone
cluded for screening. After screening of titles and abstracts, (20 mg/day, PO, for 5 days; n = 25). The trial of Zuberbier
2203 articles were excluded mainly due to irrelevant study et al.18 allocated both adults and children into a treatment
designs or research questions (e.g. not a study specific on with either loratadine (10 mg/day, PO, for 3 days, n = 44)
AU). A total of 49 reports were sought for retrieval. Two ar- until remission or a short course of prednisolone (50 mg/
ticles were not available in full text. After full-­text screening day, PO, for 3 days, n = 65), followed by loratadine until re-
of 47 articles, another 37 articles were excluded. The main mission. Table 1 presents the outcome measurements and
reasons for exclusion were, wrong outcome (n = 17), wrong treatment effects of the included studies.
publication type (n = 17) and wrong study design (n = 3)
(Table S3). A total of 10 studies describing the treatment
of AU were finally included for data extraction and quality Primary outcome: Treatment effects
assessment.15–24
Relief of pruritus
Pruritus relief was assessed in the trials of Barniol et al.,15
Study characteristics Pollack et al.16 and Palungwachira et al.17 The primary end-
point in the group of Barniol15 was ‘itch relief’ at 2 days after
Ten articles concerned RCTs.15–24 The publication year the emergency department visit, defined by a numeric rating
ranged from 199022 to 2021.17 The included studies involved scale score equal to 0–10. The ‘effect of treatment’ was as-
a total of 857 participants. The largest study consisted of 262 sessed 1 h after treatment and at 2, 5 and 21 days after dis-
participants,19 and the smallest assigned 20 participants.21 charge. The authors found that 62% of the patients in the
Eight studies included adults only (18–78 years), while two levocetirizine + prednisone group and 76% of the levoceti-
concerned both adults and children (5–86 years).18,22 Nine rizine + placebo group had an itch score of 0 (Δ −14%; 95% CI
studies were conducted at the emergency department and −31% to 4%) after 2 days.15 Also, no significant differences in
one at the outpatient Department of Dermatology.18 Two out treatment response were noted at later time points, so treat-
of the ten studies included participants with acute allergic ment was effective in both groups.
syndromes; however, only data on the participants with AU Pollack et al.16 investigated ‘severity of pruritus’ as
were included.20,23 Tables 1 and 2 summarize the character- endpoint using VAS. Itch score at Day 2 was 4.4 ± 2.2
istics of the included studies. (mean ± SD) for the control group (diphenhydramine + hy-
droxyzine + placebo) and 1.3 ± 1.3 (mean ± SD) for the
treatment group (diphenhydramine + hydroxyzine + pred-
Results of the interventional studies nisone; p = 0.0001). At 5 day the itch score was 1.6 ± 1.0
(mean ± SD) for the control group and 0.0 ± 0.0 for the
Studies assessing the efficacy of corticosteroids treatment group (p = 0.0001).16
plus antihistamines for AU treatment In the study of Palungwachira et al.,17 the primary
endpoint was the ‘change in pruritus between baseline
Four interventional studies evaluated the effective- and 1 h post treatment’. A pruritus visual analogue scale
ness of short-­course corticosteroids in addition to H1-­ (VAS)-­score25 was assessed at 15, 30 and 60 min after
antihistamines for adult AU treatment.15–18 Patients in the treatment. Pruritus relief was defined as a >2 cm decrease
study of Barniol and colleagues15 received either per os evaluation posttreatment. No differences found in the
(PO) levocetirizine (5 mg/day for 5 days; n = 50) plus pred- VAS-­scores among the chlorpheniramine + cetirizine con-
nisone (40 mg/day, PO, for 4 days) or levocetirizine (5 mg/ trol group and the pooled intervention groups chlorpheni-
day, PO, for 5 days plus placebo for 4 days; n = 50). Pollack ramine + dexamethasone + cetirizine (+prednisolone) after
et al.16 randomized two groups, which received either in- 60 min. The median difference between at 60 min was 0.14
tramuscular (IM) diphenhydramine (50 mg) in the emer- (95% CI: −1.47 to −1.75).17 No significant differences were
gency department, followed by hydroxyzine (25 mg, PO, observed after one week or month between the groups
 TA BL E 1 Characteristics of included studies assessing the effect of corticosteroids in addition to antihistamines for the management of AU.
2086

Total
Study ID Study participants Treatment interventions (drug; dose; Treatment effects (intervention vs. control;
|   

(Author, year) design (N; % F) Age mean (SD) Country Setting administration) Treatment effect assessment mean(SD))

Barniol et al.15 RCT 100 (53%) Intervention: 27 (IQR: France ED Intervention: (n = 50) 1 h after treatment Patients with itch score of 0 after 2 days: 62%
23–41) • LCZT (5 mg/day; 5 days; PO) Follow-­up: 2, 5, 15, 21 days vs. 76%; ES: −14%; 95% CI −31% to 4%
Control: 27 (IQR: 23–44) • PRED (40 mg/day; 4 days; PO) after discharge Patients with resolution of rash after 2 days:
Control: (n = 50) 70% vs. 78%; ES: −8%; 95% CI −25% to 5%
• LCTZ (5 mg/day; 5 days, PO) Patients with relapse: 30% vs. 24%; ES: −6%;
• Placebo (4 days, PO) 95% CI −11 to 23%
Patients with adverse events: 14% (n = 7) vs.
14% (n = 7)
Fatigue, sedation, dyspepsia
Pollack et al.16 RCT 43 (44%) Intervention: 27 (10) USA ED Intervention: (n = 24) 2 days and 5 days after Itch score after 2 days: 1.3 (1.3) vs. 4.4 (2.2);
Control: 26 (8) • DPH (50 mg; IM) treatment p = 0.0001
• HYZ (25 mg; every 4–8 h, PO) Itch score after 5 days: 0.0 (0.0) vs. 1.6 (1.9);
• PRED (20 mg, every 12 h; 4 days, p = 0.0001
PO) Resolution of wheal
Control: (n = 19) Type of adverse events: Sedation after HYZ
• DPH (50 mg, IM) intake
• HYZ (25 mg, every 4–8 h, PO)
• Placebo (every 12 h; 4 days, PO)
Palungwachira RCT 75 (77%) Intervention A: 31.3 (13.6) Thailand ED Intervention A: (n = 25) 15, 30, 60 min after treatment: Change in pruritus mean VAS score between 0
et al.17 Intervention B: 29.9 • CPM (10 mg; IV) Follow-­up: 7 and 30 days after and 60 min post treatment:
(10.8) • DEX (5 mg; IV) discharge Intervention A vs. Control 15 min: 4.4 (3.1–5.3)
Control: 33.2 (11.5) • CTZ (10 mg/day; 7 days; PO) vs. 5.0 (3.2–5.9); ES: −0.61; 95% CI −1.51
Intervention B: (n = 25) to 0.30
• CPM (10 mg; IV) Intervention A vs. Control 30 min: 3.1
• DEX (5 mg; IV) (2.2–4.2); ES: 0.92; 95% CI −0.53 to 2.37
• PSL (20 mg/day, 5 days, PO) Intervention A vs. Control 60 min: 1.4
Control: (n = 25) (0.6–2.9) vs. 1.3 (0.4–4.1); ES: 0.14; 95% CI
• CPM (10 mg; IV) −1.47 to 1.75
• CTZ (10 mg/day; 7 days; PO) Patients with UAS7 > 6 at 1 week:
• Placebo (10 mL; saline; IV) Intervention B vs. Control: 29.2% vs. 4.2%; ES:
29.2%; 95% CI 10.8% to 51.3%
Adverse events
Intervention A vs. Intervention B vs. Control:
17.4% (n = 4) vs. 4.2% (n = 1) vs. 0%
Transient blurred vision, dry mouth,
dyspepsia, dizziness, headache,
palpitations, perineal itching, and urinary
retention.
Zuberbier et al.18 RCT 109 (59%) 31.4 (13.7) Germany Dep. Of Intervention: (n = 65) 3, 7, 14, 21, >21 days after Patients with cessation of wheals at 3 days:
Dermatology • PSL (50 mg/day, 3 days, PO), treatment 93.8% vs. 65.9%; p < 0.001
followed by Patients with cessation of wheals at 7 days:
• LTD (10 mg/day, PO) until 3.1% vs. 15.9%; n.s.
remission No flares were noted
Control: (n = 44)
• LTD (10 mg/day, PO) until
remisssion

Abbreviations: C, control; CPM, chlorpheniramine; CTZ, cetirizine; DEX, dexamethasone; DPH, diphenhydramine; ED, emergency department; ES, effect size; HYZ, hydroxyzine; I, intervention; IM, intramuscular; IV, intravenous;
LCTZ, levocetirizine; LTD, loratadine; PO, per oral; PRED, prednisone; PSL, prednisolone; RCT, randomized controlled trial; UAS7, Urticaria Activity Score; VAS, visual analogue scale.
TREATMENTS OF ACUTE URTICARIA

14683083, 2024, 11, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/jdv.19904 by Bauman Moscow State Technical University, Wiley Online Library on [28/10/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
 TA BL E 2 Characteristics of included studies assessing the effect of antihistamines for the management of acute urticaria.

Total
Study (author, Study participants Treatment interventions
year) design (N; % F) Age mean (SD) Country Setting Effect assessment (drug; dose; administration) Treatment effects (intervention vs. control)
BADLOE et al.

19
Abella et al. RCT 262 (63%) Intervention: 39.2 USA/Canada ED/UCC 1-­and 2 h Intervention: (n = 135) Patient-­rated pruritus score change from baseline at 2 h: −1.5 (1.0)
(16.0) posttreatment, • DPH (50 mg; IV) vs. −1.6 (0.9); ES: 0.1; 95% CI −0.1 to 0.3; p = 0.35
Control: 39.0 (16.3) Follow-­up: 24, Control: (n = 127) Patient returning after discharge: 24 h: 11.1% vs. 3.9%; p = 0.04;
48 h and 28 days • CTZ (10 mg; IV) 48 h: 14.1% vs 5.5%; p = 0.02
after discharge Adverse events: Dizziness (n = 5) and nausea (n = 3)
Lin et al.20 RCT 91 (60%) 32.3 (range: USA ED Baseline, 1, 2 h after Intervention: (n = 48) Resolution of urticaria
19.6–79.40) treatment • DPH (50 mg, IV) Proportion of patients without urticaria: 91.7% vs. 73.8%; ES: 0.17;
• RAN (50 mg, IV) 95% CI 0.02 to 0.33; p = 0.02
Control: (n = 43) Number of areas involved with urticaria: I < C; p = 0.02 OR 4.7, 95%
• DPH (50 mg, IV) CI 1.2 to 22.2; p > 0.03
• Saline (IV) Adverse events: None
Pontasch RCT 20 (75%) 32 (range: 19–78) USA ED During ED visit Group 1: (n = 7) Repeat use of medication:
et al.21 Follow-­up at 10 days • DPH (25 mg/4×/day, 5 days, PO) Gr. 1 vs. Gr. 2 vs. Gr. 3: 86% vs. 50% vs. 43%
Group 2: (n = 6) Relief of symptoms at 12 h:
• FMT (20 mg/2×/day, 5 days, PO) Gr. 1:vs. Gr. 2 vs. Gr. 3: 57% vs. 17% vs. 14%
Group 3: (n = 7) Relief of symptoms at 3 days:
• CS (200 mg/4×/day, 5 days, PO) Gr. 1 vs. Gr.2 vs. Gr. 3: 86% vs. 83% 57%
Time to improvement: No significant difference among treatment
groups
Adverse events:
Gr. 1 vs. Gr.2 vs. Gr. 3: 43% vs. 50% vs. 14% Drowsiness
Moscati et al.22 RCT 93 (52%) Intervention: 25.96 USA ED Baseline and 30 mins Intervention: (n = 47) Change in itch score: −1.174 (0.996) vs. −1.489 (1.019); ns
(8.06) after treatment • DPH (50 mg, IM) Change in wheal intensity: −0.935 (0.646) vs. −0.915 (0.654); ns
Control: 26.28 (8.96) Control: (n = 46) Change in wheal extent: 1.304 (0.465) vs. 1.426 (0.5); ns
• CTD (300 mg, once, IM) Overall improvement: 2.870 (0.341) vs. 2.723 (0.452); ns
Change in sedation: 0.37 (0.61) vs. 1.085 (0.855); p < 0.0001
Runge et al.23 RCT 39 (62%) 31.7 (9.3) USA ED 30 mins, 1, and 24 h Group 1: (n = 14) Relief of urticaria:
after treatment • DPH (50 mg, IV/PO) Gr. 1 vs. Gr. 3: 30.7 (6.1) vs. 55.3 (6.5); p = 0.006
• Placebo (saline) Gr. 1 vs. Gr. 2: 30.7 (6.1) vs. 42.9 (11.0); ns
Group 2: (n = 12) Gr. 2 vs. Gr. 3: 42.9 (11.0) vs. 55.3 (6.5); ns
• CTD (300 mg, IV/PO) Clinically significant relief of urticaria:
• Placebo (saline) Gr. 1 vs. Gr. 2: 5/11 vs. 8/10; ns
Group 3: (n = 13) Gr. 1 vs. Gr. 3: 5/11 vs. 11/12; p = 0.027
• DPH (50 mg, IV/PO) Gr. 2 vs. Gr. 3: 8/10 vs. 11/12; ns
• CTD (300 mg, IV/PO) Adverse events:
Gr. 1 (n = 1) and Gr. 3 (n = 1): Burning sensation at the IV-­l ine site
Gr. 2 (n = 2): superficial thrombophlebitis 48 h after treatment
Watson et al.24 RCT 25 (56%) Intervention: 29 (9) USA ED 30 mins after Intervention: (n = 15) Change in patient-­rated pruritus:
Control: 28 (6) treatment • FMT (20 mg, IM) I: −36 mm; 95% CI −48 to −24; p < 0.0001
Control: (n = 10) C: −54 mm; 95% CI −72 to −36; p < 0.0001
• DPH (50 mg, IM) No between group differences

Abbreviations: C, control; CS, cromolyn sodium; CTD, cimetidine; DPH, diphenhydramine; ED, emergency department; FMT, famotidine; Gr, group; I, intervention; IM, intramuscular; IV, intravenous; NS, not significant; OR, odd ratio;
PO, per oral; RAN, ranitidine; RCT, randomized controlled trial; UCC, urgent care centre.
|    
2087

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2088 |    TREATMENTS OF ACUTE URTICARIA

regarding Urticaria Activity Score (UAS7), 26 itch + wheal (50 mg, IV) plus placebo (n = 14) or cimetidine (300 mg, IV)
composite score. plus placebo (n = 12) or diphenhydramine and cimetidine
(n = 13). The trial of Watson et al.24 compared intramuscular
Resolution of rash H1-­versus H2-­ antagonist, using diphenhydramine (50 mg,
Barniol et al.15 and Pollack et al.16 both assessed ‘resolution n = 10) or FMT (20 mg, n = 15).
of rash’ as secondary endpoint. In the trial by Barniol et al.15
‘resolution of rash’ was defined as 0% of total body surface
area affected by urticaria. This was found in 70% of the pa- Primary outcome: Effect of treatment
tients in the levocetirizine + PRED group compared to 78%
of those in the levocetirizine + placebo group (Δ −8%; 95% Relief of urticaria
CI −25% to 5%).15 Lin et al.,20 Runge et al.23 and Watson et al.24 assessed the
The study of Pollack et al.16 investigated ‘resolution of relief of urticaria as endpoint in their studies. Lin et al.20
rash’ by patient's description on the extent, location and studied (investigator-­assessed) ‘resolution of urticaria’ at 1
duration of rash. After the first follow-­up visit, there was and 2 h, assessed with a check-­off cartoon of body areas. The
no difference in description of rash extent between the two proportion of patients with relief of urticaria was higher in
groups. At the final follow-­up, all patients in the predniso- the diphenhydramine + ranitidine group at 2 h after admin-
lone group reported their wheals as completely resolved.16 istration. This was 25 out of 29 participants in the diphenhy-
The trial study of Zuberbier and co-­workers,18 termed dramine + ranitidine group versus 13 out of 24 participants
this outcome as ‘cessation of wheals’. This was assessed at 3, in the diphenhydramine + saline group, 0.17 (95% CI 0.02–
7, 14 and >21 days after treatment. At 3 days, 65.9% of the pa- 0.33).20 Runge et al.23 investigated clinically significant ‘re-
tients in the loratadine group and 93.8% of the patients in the lief of urticaria’ as primary outcome, this was defined as the
prednisolone + loratadine group met the primary outcome difference in the VAS-­score after treatment with a change of
(p < 0.001). Treatment was effective in both groups, although ≥25 mm compared to baseline. Relief of urticaria was assessed
prednisolone had a more rapid effect. No side effects were at 30 min after treatment and at 24–48 h after discharge. Of
observed in either of the treatment groups.18 the patients in the diphenhydramine + placebo group, 5 out
of 11 had a clinically significant mean relief score, compared
Secondary outcome: Adverse effects to 8 out of 10 patients in the cimetidine + placebo group
Barniol et al.15 reported ‘adverse effects’ in 14% (n = 7) of the and 11 out of 12 in de diphenhydramine + cimetidine group
patients, in both groups. The most common were fatigue, (p = 0.027).23 Watson et al.24 assessed ‘relief of urticaria’ as
sedation, insomnia and dyspepsia.15 Patients in the study secondary outcome defined as physician-­rated intensity of
of Pollack et al.16 who received hydroxyzine complained urticaria and body surface area affected by urticaria. The ef-
of sedation. In the study of Palungwachira et al.,17 patients fect of treatment was assessed at 30 min after treatment. The
who received additional corticosteroids (n = 5) complained famotidine group showed a decrease of 34 mm (95% CI, −47
of transient blurred vision, dry mouth, dyspepsia, dizziness, to −20, p < 0.001) in intensity of urticaria, and the diphenhy-
headache, palpitations and perineal itching.17 dramine group also showed a decrease of 34 mm (95% CI,
−56 to −13, p < 0.01). For body surface area, patients in the
Efficacy of antihistamines for the treatment of AU famotidine group showed a decrease of 20% (95% CI, −33 to
Six randomized clinical trials compared the efficacy of H1 and/ −7, p < 0.01), while in the diphenhydramine group a decrease
or H2-­antihistamines for the treatment of AU.19–24 In the study of 8% (95% CI, −17 to 0, 0.05 < p < 0.10) was found.24
of Abella et al.,19 a comparison was made between two groups
receiving H1-­antihistamines, the treatment with diphenhy- Relief of pruritus
dramine (50 mg) or treatment with less sedative cetirizine ‘Relief of pruritus’ was evaluated in the studies of Abella
(10 mg).19 Lin et al.20 randomized patients into two groups com- et al.,19 Watson et al.24 and Moscati et al.22 Abella et al.19
paring H1-­antihistamines with an additional H2-­antagonist, studied this endpoint as ‘patient-­rated pruritus score change’
a group receiving 50 mg diphenhydramine plus ranitidine from baseline to 2 h after treatment. There were no treatment
(50 mg; n = 48) and a control group receiving diphenhydramine differences found between cetirizine and diphenhydramine,
(50 mg; n = 43) plus saline. Pontasch et al.21 allocated patients 0.1 (95% CI −0.1 to 0.3, p = 0.35).19 Watson et al.24 investi-
into three groups comparing H1-­antihistamines versus H2-­ gated ‘change in patient-­rated pruritus’ as primary outcome,
antagonists versus a mast cell stabilizer. The groups received assessed by a VAS-­score, 30 min after treatment. There was a
either diphenhydramine (25 mg/day q.i.d, PO; n = 7) or famo- decrease of 36 mm in the famotidine group (95% CI, −48 to
tidine (20 mg/day b.i.d, n = 6) or cromolyn sodium (200 mg −24, p < 0.0001) and 54 mm (95% CI, −72 to −36, p < 0.0001)
q.i.d., PO; n = 7). Moscati et al.22 and Runge et al.23 compared in the diphenhydramine group, which was not significant
H1-­antihistamines (diphenhydramine) and H2-­antihistamines different between groups.24 Moscati et al.22 investigated
(cimetidine) with each other. Moscati et al.22 randomized ‘change in itching’ as primary endpoint, assessed by patients
two groups that either received diphenhydramine (50 mg, on a numeric scale from 0 to 3 defined by the difference in
IM, n = 47) or cimetidine (300 mg, IM, n = 46). Runge et al.23 score before and 30 min after treatment. Both treatments
compared three groups that either received diphenhydramine showed significant improvement of itching (p < 0.001). In the
 14683083, 2024, 11, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/jdv.19904 by Bauman Moscow State Technical University, Wiley Online Library on [28/10/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
BADLOE et al.     | 2089

diphenhydramine group, 76% of the patients reported im- Risk of bias of the included randomized
provement of pruritus compared to 87% of the patients in controlled trials
the cimetidine group.22 When comparing symptom relief of
itching, no significant differences were found between the Risk of bias assessment in the present review showed that
groups. six15–17,19,20,22 out of the ten studies had an overall judgement
of low risk of bias, while four trials18,21,23,24 were assessed
Intensity and extent of wheals to have a high risk of bias or some concerns. Details of the
Moscati et al.22 was the only study investigating ‘decrease risk of bias judgement for each study are shown in Table 3.
in wheal intensity’ as outcome measurement. This was as- A graphical representation of the overall risk of bias of the
sessed by patients on a numeric scale from 0 to 3, defined by included studies is shown in Figures 2 and 3.
the difference in score before and 30 min after the treatment. Watson et al.24 in their study, had some concerns regard-
Each group improved in intensity of wheals (p < 0.0001). No ing the randomization process due to the lack of reporting
significant difference between groups was found with regard on allocation concealment. In the study by the group of
to comparison of intensity or extent of wheals. Zuberbier et al.,18 randomization or allocation concealment
was done during the first 6 months and subsequently the
Perception of overall improvement concealment was broken. The study of Pontasch et al.21 had
‘Time to relief’ and ‘patient's satisfaction’ to the medication a high loss of follow-­up and failed in reporting the number
was assessed by Pontasch et al.21 by a scale rating of 1 (poor needed to treat, which leads to some concerns in the per-
result and unsatisfied with the medication) to 10 (recom- formance bias in this study. The exact number needed to
mending medication use). The diphenhydramine group re- treat was also not reported by the trail of Zuberbier et al.18 In
ported the highest relief (57% after 12 h, 86% after 3 days). In most of the studies, there were some concerns regarding the
the famotidine group, 17% reported relief after 12 h and 83% measurement of the data due to several patient self-­reported
after 3 days. In the cromolyn sodium group, 14% reported outcomes. Selective reporting was difficult to assess, con-
relief after 12 h and 57% after 3 days. For the patient's satis- sidering that only the study of Barniol et al.15 had a pre-
faction score on the medication, 6 out of 7 (86%) gave a score specified protocol available. The studies Abella et al.19 and
of 10 in the diphenhydramine group and 1 out of 7 in the Palungwachira et al.17 mentioned having a protocol, but this
cromolyn sodium group (14%). was not available online. Nevertheless, primary endpoints
were reported as specified in the study objectives.

Secondary outcome
DISC US SION
Adverse events
Adverse events reported in the studies that compared Due to their anti-­inflammatory activities and immuno-
H1-­antihistamines and/or H2-­ antihistamines were, dizzi- suppressive actions, the use of corticosteroids has been
ness,19 nausea,19 drowsiness,21 sedation22,24 burning sensation widely used as a treatment for acute urticaria and aller-
of IV-­line23 and thrombophlebitis.23 Dizziness (4.4%) and gic conditions. The purpose of this systematic review was
nausea (3.0%) were the most common in the trial of Abella to objectively determine the existing evidence-­based ap-
et al.,19 all occurring in the diphenhydramine group.19 In the proaches for the treatment of patients with AU. Four RCTs
study of Pontasch et al.,21 drowsiness was the most frequently assessed the efficacy of corticosteroids in addition to anti-
reported adverse events in all groups, 3 out of 6 in the famo- histamines for the management of AU. Of those, two stud-
tidine group, 1 out of 7 in the cromolyn sodium group and ies Barniol et al.15 and Palungwachira et al.17 revealed that
3 out of 7 in the diphenhydramine group.21 Moscati et al.,22 a combination of corticosteroids and antihistamines did
assessed ‘sedation’ as a primary outcome on a numeric scale not have a beneficial effect on the resolution of AU. The
from 0 to 2, defined as the difference in score before and other two studies Pollack et al.16 and Zuberbier et al.18 did
after the treatment. Diphenhydramine caused significantly find a positive effect.
more sedation than cimetidine (p < 0.0001).22 Watson and Despite the lack of evidence, a study on the demograph-
co-­workers24 investigated patient rated sedation as a second- ics of AU in emergency departments, revealed that most
ary outcome using VAS-­scores. No change (0 mm) in seda- emergency physicians, use corticosteroids in addition
tion was reported in the famotidine group (95% CI, −14 to 15, to antihistamines as a treatment for patients with AU.27
p < 0.50). The diphenhydramine group showed an increase However, it is well known that systemic corticosteroids may
of 20 mm (95% CI, −7 to 47, p < 0.10). The authors reported cause several adverse effects given their diverse mechanism
no significant difference between the groups in all second- of action, which usually are dose and time-­dependent.28
ary endpoints.24 Runge et al.23 reported burning sensation of The use of corticosteroids for short-­term treatment is often
the IV line site in one patient receiving diphenhydramine and associated with cutaneous side effects (e.g. ecchymosis,
one with diphenhydramine + cimetidine. Two patients in the skin atrophy, acne, mild hirsutism and striae). Other short-­
cimetidine group experienced superficial thrombophlebitis term side effects include electrolyte abnormalities, hyper-
48 h after treatment.23 tension, hyperglycaemia and pancreatitis.29 Long-­term
 14683083, 2024, 11, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/jdv.19904 by Bauman Moscow State Technical University, Wiley Online Library on [28/10/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
2090 |    TREATMENTS OF ACUTE URTICARIA

TA BL E 3 Risk-­of-­bias assessment per domain for included RCTs.

Risk of bias domains

Study ID D1 D2 D3 D4 D5 Overall risk of bias

15
Barniol et al. Low Low Low Some concerns Low Low
Pollack et al.16 Low Low Low Some concerns Low Low
Palungwachira et al.17 Low Low Low Some concerns Low Low
18
Zuberbier et al. High High Low Some concerns Low High
Abella et al.19 Low Low Low Some concerns Low Low
20
Lin et al. Low Low Low Some concerns Low Low
Pontasch et al.21 Low Some concerns Some concerns Some concerns Low High
22
Moscati et al. Low Low Low Some concerns Low Low
Runge et al.23 Low Low Low Some concerns Low Some concerns
24
Watson et al. Some concerns Low Low Some concerns Low Some concerns

Abbreviations: D1, bias due to randomization; D2, bias due to deviations from intended intervention; D3, bias due to missing data; D4, bias due to outcome measurements;
D5, bias due to selection of reported results.

Risk of bias domains

D1 D2 D3 D4 D5 Overall

Albella et al., 2020

Barniol et al., 2017

Lin et al., 2000

Moscati et al., 1990

Palungwachira et al., 2021

Study

Pollack et al., 1995

Pontasch et al., 1993

Runge et al., 1992

Watson et al., 2000

Zuberbier et al., 1996

Domains: Judgement
D1: Bias arising from the randomization process.
D2: Bias due to deviations from intended High
intervention. Some concerns
D3: Bias due to missing outcome data.
D4: Bias in measurement of the outcome. Low
D5: Bias in selection of the reported result.

FIGU R E 2 Risk of bias assessment summary. Review authors' judgement per risk of bias domain for each included study.

Bias arising from the randomization process

Bias due to deviations from intended interventions
High
Bias due to missing outcome data
Some concerns
Bias in measurement of the outcome
Low
Bias in selection of the reported result
Overall risk of bias

0% 25% 50% 75% 100%

FIGU R E 3 Risk of bias graph. Review author's judgement per risk of bias domain presented as percentages across all included studies.

use side-­effects are cardiovascular-­, gastrointestinal-­, en- supervision are needed in patients with pre-­existing con-
docrine-­, musculoskeletal-­, ocular-­, dermatologic-­or im- ditions, such as diabetes mellitus or hypertension to mini-
mune system related.30 Appropriate strategies and careful mize potential harm from side effects.30
 14683083, 2024, 11, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/jdv.19904 by Bauman Moscow State Technical University, Wiley Online Library on [28/10/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
BADLOE et al.     | 2091

This review also assessed the efficacy of combined treat- analysis of core outcome sets. Also, newer antihistamines
ment of antihistamines (First vs. second generation and H1 were not evaluated.
vs. H2) on the treatment of AU. In six studies that addressed
this topic, each study utilized antihistamines including, di-
phenhydramine, cetirizine, ranitidine, cimetidine and fa- C ONC LUSION
motidine. Diphenhydramine seemed to be the preferred IV
treatment for AU. Diphenhydramine is well known for its As the results of the published studies are inconsistent, the
sedating and anticholinergic adverse effects, which can limit addition of corticosteroids to an antihistamine as a treatment
its use. The latest study of Abella et al.19 found that the use for AU option needs to be further investigated. None of the
of IV cetirizine is as effective as IV diphenhydramine in the included studies analysed the progression from AU to CSU.
treatment of AU. The advantage of IV cetirizine is to be less A longer follow-­up of more than 6 weeks is needed to evalu-
sedative and it has a lower overall adverse events rate,19 but ate whether corticoid steroid use in addition to antihistamine
IV cetirizine is not available in every country. has a protective impact on the development of CSU. The lat-
The discrepancies found between the studies are most likely est guidelines on the treatment of AU are based on a limited
related to the differences in study design, sample size, lack of ­number of trials (RCTs and non-­RCT). Finally, AU recommen-
core outcome sets and the type of antihistamines used in the dations are often extrapolated from CSU. The currently avail-
trials. The trials reviewed and assessed were difficult to categor- able data does not allow us to answer the question of whether
ically compare due to the variations in study designs and un- the addition of corticosteroids to antihistamine indeed have a
clear, defined study outcomes. To compare and provide a better beneficial effect. Sufficiently powered trials are needed to ad-
understanding of the evidence-­based treatment, it is impera- dress the optimal approach, using up-­to-­date read-­outs.
tive to use standardized core outcome sets in clinical trials.31
Additionally, it has become clear that there is a need for novel AU T HOR C ON T R I BU T ION S
drugs to be introduced for the treatment of AU. Certain drugs, FMSB: Designed the protocol, designed the search strat-
which are no longer considered to be state-­of-­the-­art medica- egy, performed the search, performed screening of studies,
tions in 2023 are still being prescribed in emergency rooms performed the data collection of the included studies, per-
and outpatient settings (e.g. diphenhydramine, hydroxyzine formed the quality assessment of included studies, first re-
and chlorpheniramine). This was also evident in the review of viewer, wrote the first draft of the manuscript, revised the
the studies which were limited to the drugs listed above. The first version of the manuscript, designed the tables and fig-
currently available trials were set up to answer the question, ures, revised and approved the final version. MG: Designed
whether the addition of corticosteroid steroids to antihistamine the protocol, performed the screening of included studies,
could improve AU activity. However, statistically powered trials second reviewer, revised the first version of the manuscript,
are also required to answer the question whether the combina- revised and approved the final version. JR: Discussed the
tion of these drugs can also reduce the progression to CSU. content of the manuscript, revised the first version of the
The use of systemic steroids for treatment of inflamma- manuscript, revised and approved the final version. IKK:
tory skin disease, such as atopic dermatitis or psoriasis is Discussed the content of the manuscript, revised the first
often associated with disease flares upon cessation of ste- version of the manuscript, revised and approved the final
roids.32,33 However, this is inconclusive as it has not yet been version. JG: Contributed to the design of the protocol, dis-
studied in AU and needs to be addressed in future trials for cussed the content of the manuscript, third reviewer revised
viability. Although, the recent guideline on the management the first version of the manuscript, revised and approved the
of AU states that the use of a short course (up to 10 days) of final version.
oral corticosteroids could aid with the reduction of the dis-
ease duration or activity,1 it is currently unknown whether AC K N OW L E D G E M E N T S
steroids shorten or prolong the disease course. The authors We would like to that Prof. Dr. David Beckwée for his statis-
also mentioned that well-­designed RCTs are needed in order tical support and advice.
to argue these recommendations.
F U N DI N G I N F OR M AT ION
No funding was received for this work.
Limitations
C ON F L IC T OF I N T E R E S T S TAT E M E N T
This systematic review was performed using two major sci- The authors have no conflict of interest to declare.
entific and medical online databases. A potential limitation
is that some studies were still missed during the process DATA AVA I L A BI L I T Y S TAT E M E N T
because the reviewers excluded articles that were not avail- Data sharing is not applicable to this article as no new data
able in English, Dutch French or German or when the full were created or analysed in this study.
text was not available. Ultimately, this systematic review
was conducted on ten studies and several of these studies E T H IC A L A PPROVA L
were performed more than 20 years ago, with no conclusive No ethical approval was needed for this systematic review.
 14683083, 2024, 11, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/jdv.19904 by Bauman Moscow State Technical University, Wiley Online Library on [28/10/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
2092 |    TREATMENTS OF ACUTE URTICARIA

19. Abella BS, Berger WE, Blaiss MS, Stiell IG, Herres JP, Moellman JJ,
ORC I D et al. Intravenous cetirizine versus intravenous diphenhydramine for
Fariza M. S. Badloe https://orcid.org/0000-0002-4881-6450 the treatment of acute urticaria: a phase III randomized controlled
Martine Grosber https://orcid.org/0000-0002-7945-1028 noninferiority trial. Ann Emerg Med. 2020;76(4):489–500.
Johannes Ring https://orcid.org/0000-0001-8236-3152 20. Lin RY, Curry A, Pesola GR, Knight RJ, Lee HS, Bakalchuk L, et al.
Improved outcomes in patients with acute allergic syndromes who
Jan Gutermuth https://orcid.org/0000-0002-9252-6004
are treated with combined H1 and H2 antagonists. Ann Emerg Med.
2000;36(5):462–8.
R EFER ENCES 21. Pontasch MJ, White LJ, Bradford JC. Oral agents in the management
1. Zuberbier T, Abdul Latiff AH, Abuzakouk M, Aquilina S, Asero R, of urticaria: patient perception of effectiveness and level of satisfac-
Baker D, et al. The international EAACI/GA 2LEN/EuroGuiDerm/ tion with treatment. Ann Pharmacother. 1993;27(6):730–1.
APAAACI guideline for the definition, classification, diagnosis, and 22. Moscati RM, Moore GP. Comparison of cimetidine and diphen-
management of urticaria. Allergy. 2022;77(3):734–66. hydramine in the treatment of acute urticaria. Ann Emerg Med.
2. Kaplan AP. Chronic spontaneous urticaria: pathogenesis and treat- 1990;19(1):12–5.
ment considerations. Allergy Asthma Immunol Res. 2017;9(6):477–82. 23. Runge JW, Martinez JC, Caravati EM, Williamson SG, Hartsell SC.
3. Schaefer P. Acute and chronic urticaria: evaluation and treatment. Histamine antagonists in the treatment of acute allergic reactions.
Am Fam Physician. 2017;95(11):717–24. Ann Emerg Med. 1992;21(3):237–42.
4. Bernstein JA, Lang DM, Khan DA, Craig T, Dreyfus D, Hsieh F, et al. 24. Watson NT, Weiss EL, Harter PM. Famotidine in the treatment of
The diagnosis and management of acute and chronic urticaria: 2014 acute urticaria. Clin Exp Dermatol. 2000;25(3):186–9.
update. J Allergy Clin Immunol. 2014;133(5):1270–7. 25. Reich A, Heisig M, Phan NQ, Taneda K, Takamori K, Takeuchi S,
5. Kulthanan K, Chlawsirikajorn Y, Jiamton S. Acute urticaria: etiolo- et al. Visual analogue scale: evaluation of the instrument for the as-
gies, clinical course and quality of life. Asian Pac J Allergy Immunol. sessment of pruritus. Acta Derm Venereol. 2012;92(5):497–501.
2008;26(1):1–9. 26. Stull D, McBride D, Tian H, Gimenez Arnau A, Maurer M, Marsland
6. Nettis E, Foti C, Ambrifi M, Baiardini I, Bianchi L, Borghi A, et al. A, et al. Analysis of disease activity categories in chronic sponta-
Urticaria: recommendations from the Italian Society of Allergology, neous/idiopathic urticaria. Br J Dermatol. 2017;177(4):1093–101.
Asthma and Clinical Immunology and the Italian Society of 27. Losappio L, Heffler E, Bussolino C, Cannito CD, Carpentiere R, Raie
Allergological, Occupational and Environmental Dermatology. Clin A, et al. Acute urticaria presenting in the emergency room of a gen-
Mol Allergy. 2020;18:8. eral hospital. Eur J Intern Med. 2014;25(2):147–50.
7. Sackesen C, Sekerel BE, Orhan F, Kocabas CN, Tuncer A, Adalioglu 28. Huscher D, Thiele K, Gromnica-­Ihle E, Hein G, Demary W, Dreher
G. The etiology of different forms of urticaria in childhood. Pediatr R, et al. Dose-­related patterns of glucocorticoid-­induced side effects.
Dermatol. 2004;21(2):102–8. Ann Rheum Dis. 2009;68(7):1119–24.
8. Wedi B, Raap U, Wieczorek D, Kapp A. Urticaria and infections. 29. Buchman AL. Side effects of corticosteroid therapy. J Clin
Allergy Asthma Clin Immunol. 2009;5(1):10. Gastroenterol. 2001;33(4):289–94.
9. Sabroe RA. Acute urticaria. Immunol Allergy Clin North Am. 30. Oray M, Abu Samra K, Ebrahimiadib N, Meese H, Foster CS.
2014;34(1):11–21. Long-­term side effects of glucocorticoids. Expert Opin Drug Saf.
10. Chung WH, Chu CY, Huang YH, Wang WM, Yang CH, Tsai TF. 2016;15(4):457–65.
Taiwanese Dermatological Association consensus for the definition, 31. Williams HC, Schmitt J, Thomas KS, Spuls PI, Simpson EL,
classification, diagnosis, and management of urticaria. J Formos Med Apfelbacher CJ, et al. The HOME Core outcome set for clinical trials
Assoc. 2016;115(11):968–80. of atopic dermatitis. J Allergy Clin Immunol. 2022;149(6):1899–911.
11. Grattan CE, Humphreys F. Guidelines for evaluation and man- 32. Drucker AM, Eyerich K, de Bruin-­Weller MS, Thyssen JP, Spuls PI,
agement of urticaria in adults and children. Br J Dermatol. Irvine AD, et al. Use of systemic corticosteroids for atopic dermatitis:
2007;157(6):1116–23. International Eczema Council consensus statement. Br J Dermatol.
12. Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, 2018;178(3):768–75.
Mulrow CD, et al. The PRISMA 2020 statement: an updated guideline 33. Schwarz CW, Loft N, Andersen V, Juul L, Zachariae C, Skov L. Are sys-
for reporting systematic reviews. BMJ. 2021;372:n71. https://​doi.​org/​ temic corticosteroids causing psoriasis flare-­ups? Questionnaire for
10.​1136/​bmj.​n71 Danish Dermatologists, Gastroenterologists and Rheumatologists.
13. Ouzzani M, Hammady H, Fedorowicz Z, Elmagarmid A. Rayyan-­a Dermatology. 2021;237(4):588–94.
web and mobile app for systematic reviews. Syst Rev. 2016;5(1):210.
14. Sterne JAC, Savović J, Page MJ, Elbers RG, Blencowe NS, Boutron I,
et al. RoB 2: a revised tool for assessing risk of bias in randomised
S U PP ORT I N G I N F OR M AT ION
trials. BMJ. 2019;366:l4898. Additional supporting information can be found online in
15. Barniol C, Dehours E, Mallet J, Houze-­ Cerfon CH, Lauque D, the Supporting Information section at the end of this article.
Charpentier S. Levocetirizine and prednisone are not superior to
levocetirizine alone for the treatment of acute urticaria: a randomized
double-­blind clinical trial. Ann Emerg Med. 2018;71(1):125–131.e1.
16. Pollack CV Jr, Romano TJ. Outpatient management of acute urticaria:
How to cite this article: Badloe FMS, Grosber M, Ring
the role of prednisone. Ann Emerg Med. 1995;26(5):547–51.
17. Palungwachira P, Vilaisri K, Musikatavorn K, Wongpiyabovorn J. A J, Kortekaas Krohn I, Gutermuth J. Treatment of acute
randomized controlled trial of adding intravenous corticosteroids to urticaria: A systematic review. J Eur Acad Dermatol
H1 antihistamines in patients with acute urticaria. Am J Emerg Med. Venereol. 2024;38:2082–2092. https://doi.org/10.1111/
2021;42:192–7. jdv.19904
18. Zuberbier T, Iffländer J, Semmler C, Henz BM. Acute urticaria: clin-
ical aspects and therapeutic responsiveness. Acta Derm Venereol.
1996;76(4):295–7.