426 Practitioner's Corner
Previous Presentation
This case report was presented as an oral communication
at the AAIITO National Congress in Palermo, Italy, October
11-14, 2017.
References
1. Dervis E, Ayer M, Akin Belli A, Barut SG. Cutaneous adverse
reactions of imatinib therapy in patients with chronic myeloid
leukemia: A six-year follow up. Eur J Dermatol. 2016 Apr
1;26(2):133-7.
2. Amitay-Laish I, Stemmer SM, Lacouture ME. Adverse
cutaneous reactions secondary to tyrosine kinase inhibitors
including imatinib mesylate, nilotinib, and dasatinib. Dermatol
Ther. 2011 Jul-Aug;24(4):386-95.
3. Marin D, Marktel S, Bua M, Armstrong L, Goldman JM, Apperley
JF, et al. The use of Imatinib (STI571) in chronic myeloid
leukemia: some practical considerations. Haematologica.
2002;87(9):979-88.
4. Scott LC, White JD, Reid R, Cowie F. Management of skin
toxicity related to the use of imatinib mesylate (STI571,
GlivecTM) for advanced stage gastrointestinal stromal tumors.
Sarcoma. 2005;9:157-60.
5. Paolino G, Didona D, Clerico R, Corsetti P, Ambrifi M, Bottoni
U, et al. Skin lesions in patients treated with imatinib mesylate:
a 5-year prospective study. Cutis. 2016 Jun;97(6):E12-6.
6. Nelson RP Jr, Cornetta K, Ward KE, Ramanuja S, Fausel C, Cripe
LD. Desensitization to imatinib in patients with leukemia. Ann
Allergy Asthma Immunol. 2006 Aug;97(2):216-22.
7. Di Paolo C, Minetti S, Mineni M, Inverardi S, Lodi Rizzini F,
Cinquini M, et al. Cutaneous adverse reactions to Imatinib:
a case report of a successful slow protocol for induction of
drug tolerance. J Allergy Ther. 5: 203. doi:10.4172/2155-
6121.1000203.
8. Klaewsongkram J, Thantiworasit P, Sodsai P, Buranapraditkun
S, Mongkolpathumrat P. Slow desensitization of imatinib-
induced nonimmediate reactions and dynamic changes of
drug-specific CD4(+)CD25(+)CD134(+) lymphocytes. Ann
Allergy Asthma Immunol. 2016 Nov;117(5):514-9.
9. Castells Guitart MC. Rapid drug desensitization for
hypersensitivity reactions to chemotherapy and monoclonal
antibodies in the 21st century. J Investig Allergol Clin
Immunol. 2014;24(2):72-9.
10. Scherer K, Brockow K, Aberer W, Gooi JHC, Demoly P, Romano
A, et al. Desensitization in delayed drug hypersensitivity
reactions: an EAACI position paper of the Drug Allergy Interest
Group. Allergy. 2013;68:844-52.
Manuscript received April 23, 2018; accepted for publication
August 16, 2018.
Donatella Bignardi
Allergy Complex Unit, Ospedale Policlinico San Martino
L. R: Benzi 10
Genova, Italy
E-mail: donatella.bignardi@hsanmartino.it
J Investig Allergol Clin Immunol 2018; Vol. 28(6): 414-442
Severe Anaphylaxis With Cardiac Arrest Caused by
Prick Test With Cefuroxime
Fernandes RA1, Regateiro FS1,2, Pita J1, Ribeiro C1, Carrapatoso I1,
Todo-Bom A1, Faria E1
1
Allergy and Clinical Immunology Unit, Hospitais da Universidade
de Coimbra, Centro Hospitalar e Universitário de Coimbra,
Coimbra, Portugal
2
Instituto de Imunologia, Faculdade de Medicina, Universidade
de Coimbra, Coimbra, Portugal
J Investig Allergol Clin Immunol 2018; Vol. 28(6): 426-428
doi: 10.18176/jiaci.0305
Key words: Cardiorespiratory arrest. Cefuroxime. Cephalosporins. Severe
anaphylaxis. Skin prick tests.
Palabras clave: Paro cardiorrespiratorio. Cefuroxima. Cefalosporinas.
Anafilaxia grave. Pruebas cutáneas.
Skin tests, including the skin prick test (SPT) and
intradermal test (IDT), are useful for the in vivo diagnosis
of IgE-mediated hypersensitivity reactions to drugs. SPT is
considered a safe diagnostic approach, with only anecdotal
fatal or near-fatal reactions, most of which are caused by prick
testing with foods. No reactions caused by drugs have been
reported [1,2]. According to previous studies, the occurrence
of systemic reactions during performance of SPT is extremely
low (range, 0.02%-0.4%), and SPT-induced anaphylaxis in
particular is an exceptionally rare event [3]. We report a case
of anaphylactic shock with cardiorespiratory arrest during SPT
with cephalosporins in a patient with a history of perioperative
anaphylaxis. To the best of our knowledge, this is the first
report of anaphylaxis during SPT to cephalosporins reported
in the literature.
A 62-year-old woman was referred to our allergy
department for evaluation of perioperative anaphylactic shock.
One month previously, she had experienced an anaphylactic
reaction during cataract surgery. A few minutes after the
intravenous (IV) administration of 750 mg of cefuroxime
and 125 mg of methylprednisolone, she developed dizziness,
vomiting, labial cyanosis, tachycardia, hypotension, and
focal seizures. She was immediately intubated and treated
with intramuscular (IM) epinephrine, clemastine 1 mg IV,
methylprednisolone 125 mg IV, and volume resuscitation. The
patient had no personal or family history of atopic diseases.
Her medical history was significant for alcoholism, idiopathic
hypertension, dyslipidemia, chronic obstructive pulmonary
disease, and osteoporosis. She had been receiving long-term
therapy with enalapril/lercanidipine (10 mg/10 mg, qd),
rosuvastatin (10 mg qd), mirtazapine (30 mg qd), oxazepam
(15 mg qd), acetylsalicylic acid (100 mg, qd), inhaled
budesonide (400 µg, bid), tiotropium bromide (2.5 µg, qd)
and indacaterol (150 µg, qd).
The initial diagnostic work-up was based on in vitro assays
for determination of specific IgE to penicilloyl G, penicilloyl V,
© 2018 Esmon Publicidad
 Practitioner's Corner
amoxicillin, ampicillin, and cefaclor (CAP System FEIA,
ThermoFisher Scientific). All results were negative. The
patient’s total IgE was 152 IU/mL and basal serum tryptase
was 9.3 µg/L (reference value, <11.4 µg/L). In order to rule out
allergy to corticosteroids, SPT and IDT were performed with
betamethasone (7 mg/mL, 1:10), dexamethasone (4 mg/mL,
1:10), hydrocortisone (100 mg/mL, 1:10), methylprednisolone
(40 mg/mL, 1:1000, 1:100, 1:10), and prednisolone (25 mg/mL,
1:10). Both immediate and late results were negative for
all drugs tested. A few weeks later, SPT was performed
with cefuroxime (10 mg/mL), cefazolin (33 mg/mL), and
ceftazidime (10 mg/mL) on the volar surface of the forearm,
at concentrations known to be nonirritant [4]. Histamine and
saline solution were used as positive and negative controls,
respectively. Approximately 2 minutes after the SPT with
cephalosporins, the patient began to experience severe dyspnea
and oropharyngeal tightness, which rapidly progressed to
severe bronchospasm, cyanosis, and loss of consciousness. She
was assisted immediately with epinephrine 1 mg IM, although
she went into respiratory and cardiac arrest within seconds,
with loss of sphincter control.
Advanced life support maneuvers were initiated, and the
patient received an additional dose of epinephrine (1 mg IV),
as well as methylprednisolone 125 mg IV, clemastine 1 mg IV,
and oxygen through a nasal cannula. She was intubated and put
on respiratory life support. About 2 minutes after the cardiac
arrest, she recovered spontaneous circulation. Given the
gradually increased consciousness and resistance to intubation,
the patient was sedated with midazolam and propofol before
being transferred to the intensive care unit. She was discharged
from the unit 1 week after the reaction. A neurological
evaluation 1 month later revealed no abnormalities.
During anaphylaxis, and even for some minutes after
administration of epinephrine and recovery of heart function,
the SPT result was strongly positive for cefuroxime (~15 mm)
and negative for cefazolin and ceftazidime (histamine 6 mm).
The serum tryptase level at 1 hour and 2 hours after the onset
of symptoms was sharply elevated: 43.0 µg/L and 44.4 µg/L,
respectively. The ECG result and high-sensitivity troponin I
value (marker of myocardial necrosis) collected during the
episode were normal.
Cephalosporins are one of the most widely prescribed
classes of antibiotics owing to their broad spectrum of
activity and low toxicity profile [5]. Most allergic reactions
to cephalosporins consist of cutaneous rashes with a reported
incidence of 1%-2.8% of treatments. Anaphylactic reactions
to cephalosporins are rare, with a relative risk ranging from
1:1000 to 1:1 000 000 administrations [4]. However, cases
of fatal anaphylaxis have been reported [6,7]. Skin tests are
considered a useful tool for detecting patients with immediate
hypersensitivity to cephalosporins [5].
Given their lower risk of systemic reactions than IDT, SPT
is usually the first in vivo test to be performed in the diagnostic
work-up of suspected IgE-mediated hypersensitivity reactions.
They are easy to perform, cheap, and provide a positive/
negative response within a few minutes [8]. In a 2015 British
study on the incidence and features of systemic reactions to
SPT [9], only 1 reaction was attributed to a drug (piperacillin).
To the best of the authors’ knowledge, this is the only case
© 2018 Esmon Publicidad
427
report in the English-language literature of a severe systemic
reaction induced by SPT with cephalosporin.
Few studies have validated SPTs for the diagnosis of
immediate hypersensitivity reaction to cephalosporins [4,5],
and none have evaluated their safety with these drugs. Most
studies on the safety of these procedures are with β-lactam
antibiotics [10].
In the case we report, the acute elevation of serum
tryptase levels, which typically peak within an hour after
the onset of symptoms [3], confirms the clinical diagnosis
of an anaphylactic reaction and rules out a variety of other
conditions that could have led to cardiorespiratory arrest
(eg, severe asthma exacerbations, pulmonary embolism, and
cardiovascular events). In this particular case, the patient’s
comorbidities could have contributed to the severity of
anaphylaxis.
Normal basal serum tryptase helps to rule out the presence
of underlying systemic mastocytosis.
As reported elsewhere [3], the present case shows that
a minimally invasive technique such as SPT is capable
of inducing severe anaphylactic reactions in predisposed
individuals. When performing skin tests, clinicians should
be aware of this risk and must be capable of diagnosing and
treating subsequent reactions. The case further stresses that
these procedures should only be performed by trained staff
and in settings equipped to assess and manage anaphylaxis.
Funding
The authors declare that no funding was received for the
present study.
Conflicts of Interest
The authors declare that they have no conflicts of interest.
References
1. Blanton W, Sutphin A. Death during skin testing. Am J Med
Sci. 1949;217:169.
2. Harris M, Sure N. Sudden death due to allergy tests. J Allergy.
1950;21:208-16.
3. Syrigou E, Syrigos K. Anaphylaxis during skin prick testing for
amoxicillin. J Allergy Clin Immunol Pr. 2014;2(4):478-9.
4. Dickson S, Salazar K. Clin Rev Allerg Immunol. 2013;45:131-
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5. Yoon S, Park S, Kim S, Lee T, Lee Y, Kwon H, et al. Validation
of the cephalosporin intradermal skin test for predicting
immediate hypersensitivity: a prospective study with drug
challenge. Allergy Eur J Allergy Clin Immunol. 2013;68:938-
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6. Spruill FG, Minette LJ, Sturner WQ. Two Surgical Deaths
Associated With Cephalothin. JAMA. 1974;229(4):440-1.
7. Pumphrey RSH, Davis S. Under-reporting of antibiotic
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1999;353(9159):1157-8.
8. Liccardi G, D’Amato G, Canonica W, Salzillo A, Piccolo A,
Passalacqua G. Systemic reactions from skin testing: literature
review. J Allergol Clin Immunol. 2006;16(2):75-8.
J Investig Allergol Clin Immunol 2018; Vol. 28(6): 414-442
428 Practitioner's Corner
9. Sellaturay P, Nasser S, Ewan P. The incidence and features
of systemic reactions to skin prick tests. Ann Allergy Asthma
Immunol. 2015;115:229-33.
10. Antico A, Pagani M, Compalati E, Vescovi PP, Passalacqua G.
Risk assessment of immediate systemic reactions from skin
tests with β-lactam antibiotics. Int Arch Allergy Immunol.
2011;156(4):427-33.
Manuscript received June 12, 2018; accepted for publication
August 17, 2018.
Rosa Anita Fernandes
Serviço de Imunoalergologia, Centro Hospitalar e
Universitário de Coimbra
Praceta Prof. Mota Pinto, 3000-075 Coimbra
E-mail: rosa.fernandes.alergo@gmail.com
J Investig Allergol Clin Immunol 2018; Vol. 28(6): 414-442
Peripheral Eosinophil Counts Correlate With Nasal
Eosinophil Counts in Patients With Rhinitis
Ciprandi G1, Varricchio A2, Tajana G3, La Mantia I4, Tommasino C5
1
Associazione Italiana Vie Aeree Superiori, Naples, Italy
2
UOSD di Video-Endoscopia delle VAS, P.O. San Gennaro - Asl
Napoli1-centro, Naples, Italy
3
Anatomy and Embriology, University of Salerno, Salerno, Italy
4
ENT Department, University of Catania, Catania, Italy
5
UO Patologia Clinica, P.O. San Gennaro - Asl Napoli1-centro,
Naples, Italy
J Investig Allergol Clin Immunol 2018; Vol. 28(6): 428-430
doi: 10.18176/jiaci.0306
Key words: Eosinophils. Nose. Blood. Cytometry. Rhinitis.
Palabras clave: Eosinófilos. Nariz. Sangre. Citometría. Rinitis.
Eosinophilic inflammation affecting the nose indicates a
TH2 immune response, which is typical in allergic rhinitis and
in nonallergic rhinitis with eosinophils (NARES), as well as
in eosinophilic asthma [1]. Nasal cytology is a convenient
method that is very useful in clinical practice, mainly in the
diagnostic and prognostic work-up of patients with rhinitis [2].
In addition, it has been reported that the nasal eosinophil count
correlates better with symptom severity and IgE level [3,4].
In their cross-sectional study of adults with moderate-
severe asthma, Amorim et al [5] demonstrated a convincing
association between nasal and sputum eosinophilia and a
link between the former and bronchodilator response, ie,
postsalbutamol FEV1. These results agree with those of recent
studies that showed close similarities in tissue inflammatory
changes in asthma and rhinitis, further supporting the
concept that the upper and the lower airways should be
considered a single entity influenced by common physiologic
processes, namely, the one-airway hypothesis [6]. Therefore,
the evaluation of upper airway inflammation may provide
additional insight into lower airway involvement and suggests
that evaluation of nasal eosinophilia could be a surrogate
for sputum analysis in these patients. In other words, nasal
eosinophils may mirror bronchial eosinophils, thus enabling
the nose to be considered the window of the bronchi.
Another pathway for indirect evaluation of bronchial
eosinophils is through blood eosinophils. Peripheral
eosinophils have been reported to be a reliable surrogate
biomarker for phenotyping type 2 asthma [7].
Therefore, we tested the hypothesis of whether peripheral
eosinophil count is correlated with nasal eosinophil counts.
To verify this possibility, we compared nasal eosinophils with
blood eosinophils in a group of patients with rhinitis in a real-
world setting. The study sample comprised 41 consecutive
patients (23 males, 18 females; mean age, 38.7 years) attending
a rhinology clinic who were enrolled on 2 consecutive days.
All patients underwent a through otorhinolaryngologic
examination (including endoscopy, nasal scraping, and nasal
© 2018 Esmon Publicidad