Received: 13 October 2022 Accepted: 26 March 2023

DOI: 10.1111/pde.15322

Pediatric
Dermatology

Concurrent acute generalized exanthematous pustulosis

in siblings

Sumiti Pareek MBBS | Alpana Mohta MD | Bhikham Chand Ghiya MD |

Yogesh Kumar MBBS

Department of Dermatology, Venereology and

Leprosy, Sardar Patel Medical College,
Bikaner, India
Correspondence
Alpana Mohta, Department of Dermatology,
Venereology and Leprosy, Sardar Patel
Medical College, Bikaner, India.
Email: dralpanamohta10@gmail.com
Abstract
Acute generalized exanthematous pustulosis (AGEP) is a rare severe cutaneous
adverse reaction triggered in most cases by drugs. It is characterized by abrupt onset
and rapid evolution of fields of sterile pustules on an erythematous background. The
role of genetic predisposition in this reactive disorder is being explored. We report
the simultaneous occurrence of AGEP in two siblings after being exposed to the
same drug.

KEYWORDS
acute generalized exanthematous pustulosis, beta-lactams, drug eruptions, penicillin G, psoriasis

1 | I N T RO DU CT I O N personal history of psoriasis. On examination, there were innumerable

Acute generalized exanthematous pustulosis (AGEP) is a rare severe
cutaneous adverse reaction (SCAR), affecting 1–5 new patients per
million population every year.1 Though the mean age of onset as
reported by the EuroSCAR study is 56 years,2 it may also occasionally
affect children with reported incidence as low as 1 per million children
3
per year. It is characterized by an abrupt onset of numerous, sterile,
non-follicular pustules overlying an erythematous base, triggered by
drug ingestion in >90% of the cases. While a possibility of genetic pre-
disposition in AGEP has been speculated, there has not been any con-
firmation. We report a case of two siblings who developed AGEP
concurrently shortly after initiating the same medication.
2 | CASE REPORT
A 13-year-old female presented with generalized erythema and pus-
tules accompanied by fever. Five days prior she had taken oral penicil-
lin G (400,000 units, 4 times for 1 day) for fever and upper respiratory
tract symptoms. Twenty-four hours later, she developed intense pruri-
tus and a generalized burning sensation, and the medication was dis-
continued. This was followed by the development of generalized
erythema with overlying pustules lesions on her trunk, which rapidly
spread to involve the rest of her body. There was no family or
generalized non-follicular pustules on an erythematous background,
coalescing to form sheet-like areas in the axillary and inframammary
creases and on the face (Figure 1). Facial edema was present; lymph-
adenopathy was absent. There was erythema of the oral mucosa while
the rest of the mucosal sites were uninvolved. The patient had a fever
of 102 F (38.9 C) at presentation. Laboratory investigations revealed
a leukocyte count of 36,000/mm3 and absolute neutrophil count of
25,000/mm3.
The day following her admission, her 8-year-old brother pre-
sented with a similar history and milder rash (Figure 2). Pustules were
less widespread and erythema less intense in comparison with his sis-
ter. Mucosal surfaces were uninvolved. He had a leukocyte count of
19,000/mm3 and absolute neutrophil count of 13,000/mm3. He had
also received oral penicillin G on the same day as his sister. There was
no history of past exposure to penicillin G in either sibling. Antistrep-
tolysin O (ASO) titer and throat and blood cultures were negative for
both children.
On histopathological examination of lesional biopsies taken from
both siblings, subcorneal cleavage was noted with abundant neutro-
phils. Spongiosis was seen throughout the epidermis and there was
papillary dermal edema. Within the dermis there was moderate inter-
stitial and perivascular infiltrate of lymphocytes and neutrophils
(Figure 3). Based on the clinical presentation and histopathology, the
diagnosis of AGEP was made.

Pediatric Dermatology. 2023;40:1101–1103. wileyonlinelibrary.com/journal/pde © 2023 Wiley Periodicals LLC. 1101

1102 Pediatric
Dermatology
F I G U R E 1 Non-follicular pustules on an erythematous
background on the face and neck of the 13-year-old female.
Both patients were treated with systemic corticosteroids and sup-
portive therapy with rapid resolution of lesions with desquamation
over the next 5–6 days.
3 | DISCUSSION
Acute generalized exanthematous pustulosis is a SCAR characterized
by rapid development of sterile, non-follicular pustules on an ery-
thematous base, with a predilection for flexural sites. The cutaneous
lesions usually develop within 48 h of ingestion of the culprit drug.
While drugs, such as pristinamycin, aminopenicillins, quinolones,
hydroxychloroquine, sulfonamides, terbinafine and others constitute
the most common causes, infections (mycoplasma, parvovirus B19,
cytomegalovirus and others), hypersensitivity to mercury, spider bite,
chronic myeloid leukemia and pregnancy have also been suggested to
cause AGEP.2 These agents trigger a T-cell mediated neutrophil-rich
type IV hypersensitivity reaction that ultimately leads to the formation
of the characteristic pustules.4 Genetic predisposition may also con-
tribute, either in response to a drug or an infectious agent. Human
leukocyte antigens B51, DR11, and DQ3 are found to be associated
with AGEP.5 Moreover, interleukin-36 RN (IL-36RN) pathogenic vari-
ants may also have a role in the triggering of pustular phenotypes
PAREEK ET AL.
F I G U R E 2 Pustules with a predilection for the groin of the male
sibling, with areas of desquamation.
such as AGEP and generalized pustular psoriasis (GPP) after drug
ingestion.6 IL-36 RN pathogenic variants result in decreased or inef-
fective production of IL-36 receptor antagonist (IL-36Ra) which in
turn leads to an uninhibited IL-36 pathway, culminating in overpro-
duction of IL-6, IL-8, IL-1a, and IL-1b. All these cytokines might pre-
dispose to pustular eruptions.7
The diagnosis of AGEP is mainly clinical, substantiated by typi-
cal histopathological findings. Upon withdrawal of the culprit
agent, it is a self-limiting disease that resolves mostly with
supportive care.
4 | CONC LU SION
Acute generalized exanthematous pustulosis is a SCAR with a fairly
good prognosis. Genetic predisposition through inherited gene muta-
tions may play a contributory role in precipitating the disease upon
exposure to any of the various causative agents. This report supports
the possibility of a genetic basis in some cases of AGEP.
PAREEK ET AL.
F I G U R E 3 Subcorneal pustule with abundance of neutrophils;
epidermal spongiosis; edematous papillary dermis; perivascular
lymphocytic and neutrophilic infiltrate (hematoxylin and eosin, 100).
CONF LICT OF IN TE RE ST ST AT E MENT
The authors declare no conflicts of interest.
DECLARATION OF PATIENT CONSENT
The authors certify that they have obtained all appropriate patient
consent forms. In the form the patient(s) has/have given his/her/their
consent for his/her/their images and other clinical information to be
reported in the journal. The patients understand that their names and
Pediatric 1103
Dermatology
initials will not be published and due efforts will be made to conceal
their identity, but anonymity cannot be guaranteed.
OR CID
Alpana Mohta https://orcid.org/0000-0001-7526-2089
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How to cite this article: Pareek S, Mohta A, Ghiya BC,
Kumar Y. Concurrent acute generalized exanthematous
pustulosis in siblings. Pediatr Dermatol. 2023;40(6):1101‐1103.
doi:10.1111/pde.15322