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Received: 22 July 2020    Accepted: 4 August 2020

DOI: 10.1111/pai.13350

SUPPLEMENT ARTICLE

Acute urticaria in the infant

Domenico Minasi1 | Sara Manti2  | Fernanda Chiera3 | Amelia Licari4  |

Gian Luigi Marseglia4

1
Pediatric Unit, Grande Ospedale
Metropolitano, Reggio Calabria, Italy Abstract
2
Pediatric Respiratory Unit, Department Urticaria is a mast cell-driven disease presenting with wheals, angioedema, or both.
of Clinical and Experimental Medicine,
Acute urticaria (AU) lasts < 6 weeks. AU is a not common condition in newborns
San Marco Hospital, University of Catania,
Catania, Italy and infants since they are showing an immune system functionally insufficient. In
3
Pediatric Unit, Maternal Infant Department, newborns and infants, AU is typically generalized and featured by large, annular, or
Azienda Sanitaria Provinciale Crotone,
Crotone, Italy
geographic plaques, often slightly raised. The clinical features of the disease depend
4
Pediatric Clinic, Pediatric Department, on the peculiar structure of neonatal and infant skin. A careful morphological ex-
Policlinico San Matteo, University of Pavia, amination of the lesions is essential to differentiate AU from other skin eruptions
Pavia, Italy
that may have overlapping features and to treat it adequately. The second-generation
Correspondence antihistamines are the first-line treatment of AU; however, only antihistamines with
Sara Manti, Pediatric Respiratory Unit,
Department of Clinical and Experimental proven efficacy and safety should be used in newborns and infants. Corticosteroids
Medicine, San Marco Hospital, University of may be added in severe cases.
Catania, Via Santa Sofia 78, 95123, Catania,
Italy.
Email: saramanti@hotmail.it KEYWORDS

acute urticaria, angioedema, diagnosis, differential diagnosis, infant, newborn

Editor: Philippe Eigenmann

1 |  I NTRO D U C TI O N 2 | E TI O LO G Y A N D PATH O PH YS I O LO G Y

Urticariais a common disease characterized by the development Several mechanisms have been recognized to be involved into the eti-
of wheals (hives), angioedema, or both.1 Urticaria can either occur ology of AU in newborns and infants, including direct mast cell activa-
acutely or evolve in a chronic form. By the duration of illness, it tion, innate immunity (eg, complement, Toll-like receptors, cytokines,
is classified into acute urticaria (AU), lasting less than six weeks, chemokines, opioids) involvement, immunoglobulin E (IgE)-mediated
or chronic urticaria (CU), lasting more than six weeks. AU is a not reactions, and immune events mediated by xenobiotics (haptens,
common condition in newborns and infants since they are show- drugs).4,5 Mast cell activation leads to the release of histamine and
ing an immune system functionally insufficient. Epidemiological other inflammatory mediators, thus, resulting in sensory nerve stimu-
data report a prevalence of AU ranging from 1% to 16.2%. 2,3 lation (pruritus), vasodilatation (erythema), extravasation (edema), and
However, they do not provide reliable indications for the infant recruitment of other immune cells (infiltrate). Urticaria or itch without
since the current literature data include pediatric patients of vari- angioedema may be caused by non-histaminergic autoinflammatory
ous age of life despite the causes and clinical characteristics of mechanisms involving the cryopyrin and interleukin (IL)-1 pathway.
the AU are different in infants and young children. Moreover, AU Non-histaminergic angioedema is related to bradykinin and fibrino-
in infants must be differentiated from other skin eruptions that lytic dysregulation, as well as primary defects in vascular integrity.4,5
may have overlapping features and, therefore, be diagnosed and Common causes or triggers of AU in children include infections,
treated adequately. allergic reactions, physical stimuli, and systemic diseases.1 Mild

© 2020 European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd

Pediatr Allergy Immunol. 2020;31(Suppl. 26):49–51.  wileyonlinelibrary.com/journal/pai |

    49
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50       DOMENICO et al.

infections, often associated with drug therapy, appear to be the

most frequent causes of AU in infants, as documented in over 40%
Key messages
of the cases. The infectious agents commonly associated with AU are
Acute urticaria (AU) is a not common condition in new-
mainly viruses such as Rhinovirus, Rotavirus, Epstein-Barr, Adenovirus,
borns and infants since they are showing an immune sys-
Hepatitis virus (A, B, C) Herpes simplex, Human Immunodeficiency Virus
tem functionally insufficient. Compared to the pediatric
but also bacteria such as Mycoplasma pneumonia and Chlamydia
population, the causes and clinical characteristics of AU
pneumonia.1
are different in infants and young children. AU in infants
Less frequently, foods such as milk, egg, peanut, wheat, soy, fish,
must be differentiated from other skin eruptions that may
and shellfish can cause AU in sensitized infant and young child, and,
have overlapping features and to be diagnosed and treated
sometimes, AU can be part of a more serious anaphylactic reaction.
adequately. The second-generation antihistamines are the
Even ß-lactams and non-steroidal anti-inflammatory drugs and vac-
1 first-line treatment of AU. Corticosteroids may be added
cines are referred to as triggers of AU in both infants and children.
in severe cases. Parents need reassurance that AU is not
a life-threatening disease, and the prognosis is generally
good.
3 | C LI N I C A L PR E S E NTATI O N

Acute urticaria in infants is typically generalized and featured by large,

annular, or geographic plaques, often slightly raised.6 Moreover, edema Differently to AU, erythema multiforme is not itchy and shows
is commonly found in the dermal layer.6 In this regard, angioedema, de- persistent target lesions with a central papule, blister, purpura, or
fined as a sudden, pronounced swelling of the submucosal or subcuta- ulcer.8,9
neous tissue, involving areas such as the lips, eyelids, auricles, scrotum, Serum sickness-like reactions (SSLRs) refer to hypersensitivity
throat, back of the hands and feet, is commonly associated with AU reaction that has symptoms similar to those of serum sickness but
up to 50% of cases.5 Angioedema may sometimes be painful but not in which immune complexes are not found. Similarly to AU, the skin
itching, and its resolution is slower than wheals, lasting up to 72 hours.5 eruption presents erythematous, annular, and edematous plaques.
The clinical presentation of the disease depends on the structure and Generally, it occurs in preschool children. The onset of symptoms
6
peculiar characteristics of the skin of neonate and infant. It is usually ranges from several days up to three weeks after taking medications,
soft and smooth, thin, and lacking protective flora. The microvascula- and it is accompanied by systemic symptoms such as fever, arthral-
ture network is poorly developed, and a decreased cohesion between gia, and lymphadenopathy. The drugs most commonly associated
epidermis and dermis, as well as low content in collagen and elastic with this condition are cefaclor and other cephalosporins, penicillins,
6
fibers, has been also detected. Therefore, functionally, the skin is pre- sulfonamides, and macrolides.8,9
disposed to higher heat, transepidermal water loss, and drug and toxin An urticarial rash starting at a very early age, non-pruritic, fluc-
absorption.6 A careful morphological examination of the lesions is es- tuating irregularly, and unresponsive to antihistamine therapy can be
sential to make the diagnosis and to differentiate the AU from other the first sign of chronic infantile neurologic cutaneous and articular
similar clinical pictures as acute hemorrhagic edema of infancy, urti- (CINCA) syndrome.8,9
caria multiforme, erythema marginatum, erythema multiforme, serum The sweet syndrome is a neutrophilic dermatosis caused by a
sickness-like reaction, chronic infantile neurologic cutaneous and ar- type IV immune-mediated reaction and triggered by infections or
ticular (CINCA) syndrome, and sweet syndrome.7-9 medications. This condition is a reactive process characterized by
Acute hemorrhagic edema of infancy, or Finkelstein's or the abrupt onset of tender, erythematous papules that coalesce
Seidlamayer's disease, is a small vessel leukocytoclastic vasculitis to form plaques, often associated with fever. The pathogenesis of
that is typically associated with target-like or cockade appearance sweet's syndrome is multifactorial and remains to be definitively es-
plaques, red to purpuric lesions with a necrotic or bullous center. tablished. In children, it has been more commonly associated with
The cutaneous manifestations appear predominately over the ears, bacterial or viral upper airway infections. The sweet syndrome can
cheeks, and extremities.8,9 also be a sign of immunodeficiency or autoinflammatory disease.
The acute and transient onset of blanchable, annular, polycy- Histopathology demonstrates dermal edema, a neutrophil-predomi-
clic, erythematous, itching wheals with ecchymotic centers in as- nant infiltrate, and leukocytoclastic without true vasculitis.10
sociation with angioedema are suggestive of urticaria multiforme,
a benign cutaneous hypersensitivity reaction predominantly
histamine-mediated.8,9 4 | D I AG N OS I S A N D TR E ATM E NT
Erythema marginatum is a non-painful, transient, migrant, rarely
pruritic rash. It occurs over the trunk and in the upper arms and In addition to an accurate anamnesis, a careful morphological ex-
thighs, but never on the face. Erythema marginatum is characteristic amination of the characteristics of wheals, typically itchy, migrating,
of rheumatic fever and can also precede or accompany hereditary fading with finger pressure, duration and pattern of recurrence of le-
angioedema, although it can also occur independently.8,9 sions (less than 24 hours with episodes lasting less than six weeks), the
DOMENICO et al. |
      51

number, shape, size, site, and distribution of lesions are essential to ORCID
making the correct diagnosis. Laboratory tests should be performed Sara Manti  https://orcid.org/0000-0002-7664-3083
only when history and clinical data suggest an eliciting trigger or an Amelia Licari  https://orcid.org/0000-0003-3662-0159
underlying disease, to avoid re-exposure to relevant causative factors Gian Luigi Marseglia  https://orcid.org/0000-0002-1773-6482
and/or confirm their role in the pathogenesis.1 The second-generation
antihistamines are the first-line treatment of au, but only antihista- REFERENCES
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AU T H O R C O N T R I B U T I O N
Sara Manti: Writing-original draft (equal). Domenico Minasi:
Conceptualization (equal); Supervision (equal). Fernanda Chiera: How to cite this article: Minasi D, Manti S, Chiera F, Licari A,
Writing-original draft (equal). Gian Luigi Marseglia: Supervision Marseglia GL. Acute urticaria in the infant. Pediatr Allergy
(equal). Amelia Licari: Writing-review & editing (equal). Immunol. 2020;31(Suppl. 26):49–51. https://doi.org/10.1111/
pai.13350
PEER REVIEW
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