528 Indian Journal of Pharmacology | October 2013 | Vol 45 | Issue 5

Hypersensitivity due to ceftriaxone mimicking measles

in a child
Russelian Arulraj, Chandrasekaran Venkatesh, Nanda Chhavi, Palanisamy Soundararajan
Drug W atch
Department of Pediatrics,
Mahatma Gandhi Medical
College and Research Institute,
Pillaiyarkuppam,
Puducherry - 607 402, India
Received: 16-05-2013
Revised: 15-06-2013
Accepted: 07-07-2013
Correspondence to:
Dr. Chandrasekaran Venkatesh,
E-mail: cvenkatesh@hotmail.com
ABSTRACT
Ceftriaxone is a commonly used antibiotic in children for various infections like
respiratory tract infection, urinary tract infection and enteric fever. Hypersensitive
reactions following ceftriaxone therapy are uncommon but are potentially life-
threatening. The rash can resemble viral exanthems and may lead to a delay in the
recognition and prompt treatment. Here we report a 7-year-old boy who presented
with fever and rash with emphasis on recognizing ceftriaxone hypersensitivity and its
management.
KEY WORDS: Ceftriaxone allergy, child, hypersensitivity, maculopapular rash
Introduction
Rashes due to drugs are commonly encountered in
hospitalized children following antibiotics like penicillins,
sulfonamides and cephalosporins. Penicillins and cephalosporins
are the two most common antibiotics that cause a life threatening
IgE mediated reaction. Temporal association between drug
administration and the rash is helpful in recognizing them and
in ruling out other causes. We report a 7-year-old boy who had
a rash following parenteral ceftriaxone which mimicked that
of a measles rash.
Case Report
A 7-year-old boy was brought with a history of fever of
four days duration with cough and cold. The boy was earlier
treated with an injection outside by a private practitioner. On
examination, he was toxic with high fever of 102 F, congestion
of eyes and throat with maculopapular rash over his face and
neck [Figure 1]. He was tachypneic with bilateral crepitations
and decreased breath sounds in the right infrascapular
region. He was admitted and treated with injection ampicillin
for the respiratory infection. On the next day, the rashes
increased and appeared on the chest and upper extremities
with increasing congestion of eyes. He was thought to have
measles as he had contact with a person who had similar
illness few weeks back near his home. He was treated with
vitamin A, oxygen by face mask, nebulized salbutamol and
intravenous fluids. Since fever spikes were persistent and
TLC was elevated (21,000/cu.mm) with neutrophilia (90%),
antibiotics were changed to injection ceftriaxone after test
dose. After a period of two hours he was found to have
increasing rashes with audible wheeze, loose stools and
vomiting. By this time the rash was found throughout his
body with clearing from face. Salbutamol nebulizations were
increased in frequency and the child was monitored closely.
Over the next eight hours child became better, was able
to sit up comfortably with minimal distress and he was taking
oral feeds. The rashes appeared less prominent. He received
the second dose of injection ceftriaxone that afternoon and
following that he felt dizzy, vomited and began to have distress.
His rash once again increased and became prominent, this time,
throughout the entire body involving the face with urticarial lesions
in-addition to macula-papular lesions [Figure 2]. He appeared red
and was warm with itching all over the body, especially around
his ears. Drug allergy was suspected and was promptly treated
with oxygen, parenteral pheniramine maleate, dexamethasone,
and nebulization with salbutamol. Injection ceftriaxone was
discontinued. Within half an hour, his breathing became normal
and his rashes disappeared. This time the diagnosis was clear
and the history was re-visited. On the fourth day of illness, the
boy had received injection ceftriaxone by a local practitioner
following which the rash had appeared. He had previously been
treated with injection cefotaxime and ampicillin without having
any reactions to them. There was history of wheezing without
fever in the past and signs of allergic rhinitis and conjunctivitis
which were of mild intermittent type. He had received one dose
of measles vaccine at ten months of age. There was no family
history of allergy. He was observed for further 24 hours during
which he was totally asymptomatic and was discharged on oral
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DOI: 10.4103/0253-7613.117756
Arulraj, et al.: Ceftriaxone hypersensitivity
529 Indian Journal of Pharmacology | October 2013 | Vol 45 | Issue 5
azithromycin and prednisolone for 5 days. On follow-up a week
later, the boy was totally well and asymptomatic.
Discussion
The boy reported here had coryza, congestion of eyes
and rashes on the fourth day of illness progressing from face
down-ward to involve the trunks and extremity with history
of contact with measles. However, the boy did not have Koplik
spots. The rash became more prominent on the face, trunk
and upper extremities after another dose of ceftriaxone
which was given by us in the hospital. At that time, drug
allergy was not thought of and child was managed as measles
with bronchopneumonia. It was only after the second dose
of ceftriaxone in the hospital, the boy had all the classic
features of histamine mediated reaction which was promptly
recognized and treated. The boy did not show any reaction
to ceftriaxone test dose, which was misleading. Peripheral
eosinophilia which is commonly seen in drug allergy was also
not seen in the patient. On Naranjo causality analysis, a score
of 9 was obtained which indicates a definite adverse drug
reaction to injection ceftriaxone.
The clinical manifestations of drug allergy are quite
varied with different manifestations in different people
based on risk factors like age, gender, and genotype, route
of administration and presence of certain viral infections.
Rashes resembling exanthematous illness are known to
occur following exposure to antibiotics like penicillins,
cephalosporins and sulfonamides. Cephalosporin induced
reactions may be immediate or non immediate depending on
the time of occurrence of symptoms after the administration
of the drug.
[1]
Immediate reactions occur within one hour of
administering the drug and are characterized by the presence
of urticaria and/or angioedema, anaphylactic shock, rhinitis
and bronchospasm and are mediated by IgE. Non immediate
reactions are characterized by maculopapular or morbilliform
appearing rashes and delayed appearance of urticaria which
was seen in present case. The pathogenesis of non immediate
reactions is poorly understood.
[1]
Cross reactivity is also
known to occur between the cephalosporins and penicillins
and within cephalosporins. The degree of cross reactivity is
determined by the similarity of beta-lactam side chain that
is shared by the cephalosporins among themselves as well
as among penicillins and is largely IgE mediated.
[2]
In the
present case, cefotaxime and ampicillin had been tolerated
in the past suggesting that the reaction was due to selective
hypersensitivity only to ceftriaxone which has also been
reported in literature.
[3]
In allergy to cephalosporins, skin testing may reveal
negative results as had happened in the present case
because native compound is used for skin testing. The allergic
manifestations are due to a breakdown compound, formed
during drug metabolism.
[2]
In such instances drug challenge
serves as the gold standard in ruling out drug allergy
[4]
which
we had inadvertently done in our case. Another safe way
of diagnosing cephalosporin induced maculopapular rash
is to use enzyme linked immunospot assay to estimate the
cephalosporin specific gamma interferon, interleukin (IL)-5
and IL-10 release from peripheral blood mononuclear cells.
[5]
The advantage of this test is that it can diagnose recent as
well as remote allergy.
Conclusion
In sick children with rash who require antibiotics, care must
be taken to recognize drug rash and to treat them promptly.
Selective hypersensitivity to ceftriaxone without cross-reactivity
to other cephalosporins or penicillins can occur in children.
Non-immediate reaction to ceftriaxone is known to cause a
rash similar to measles. Skin testing has a limited value in the
diagnosis of ceftriaxone allergy and should not be relied upon
to rule out allergy.
References
1. Romano A, Gaeta F, Valluzzi RL, Alonzi C, Viola M, Bousquet PJ.
Diagnosing hypersensitivity reactions to cephalosporins in Children. Pediatrics
2008;122:521-7.
2. Pichichero ME. Areview of evidence supporting the American Academy of
Pediatrics recommendation for prescribing cephalosporin antibiotics for penicillin
allergic patients. Pediatrics 2005;115:1048-57.
3. Romano A, Torres MJ, Namour F, Mayorga C, Artesani MC, Venuti A, et al.
Immediate hypersensitivity to cephalosporins. Allergy 2002;57(Suppl 72):52-7.
4. Bousquet PJ, Gaeta F, Bousquet-Rouanet L, Lefrant JY, Demoly P, Romano A.
Provocation tests in diagnosing drug hypersensitivity. Curr PharmDes 2008;14:2792-802.
5. Tanvarasethee B, Buranapraditkun S, Klaewsongkram J. The potential of using
enzyme-linked immunospot to diagnose cephalosporin-induced maculopapular
exanthems. Acta Derm Venerol 2013;93:66-9.
Figure 1: Maculopapular rash on the face at admission Figure 2: Urticarial and maculopapular rash after second dose of
Injection ceftriaxone
Cite this article as: Arulraj R, Venkatesh C, Chhavi N, Soundararajan P.
Hypersensitivity due to ceftriaxone mimicking measlesin a child. Indian J
Pharmacol 2013;45:528-9.
Source of Support: Nil, Conict of Interest: No.
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