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Severe Anaphylactic Reaction to Ibuprofen in a Child With Recurrent Urticaria

Pediatrics

October 2007
120(3):e742-4

DOI:10.1542/peds.2006-2634

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PubMed

Authors:

Woei Kang Liew

KK Women's and Children's Hospital

Mona Iancovici Kidon

Tel Aviv University

Wen Chin Chiang

KK Women's and Children's Hospital

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An acute anaphylactic reaction after a conventional antipyretic dose of ibuprofen was diagnosed in a child with allergic rhinitis, recurrent idiopathic urticaria, and nonimmunologic cross-reactive hypersensitivity to nonsteroidal antiinflammatory drugs and acetaminophen. The patient reported several previous, mild (isolated cutaneous) hypersensitivity reactions after exposure to acetaminophen or ibuprofen. There was no evidence of an underlying inflammatory disease except as described above. Patients with chronic or recurrent idiopathic urticaria and those with atopic disease represent groups at increased risk of nonsteroidal antiinflammatory drug hypersensitivity. Mild hypersensitivity reactions to acetaminophen and/or ibuprofen may precede subsequent, more-severe adverse reactions. Risks and benefits of continued use of nonsteroidal antiinflammatory drugs in these children should be carefully considered.

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DOI: 10.1542/peds.2006-2634

2007;120;e742Pediatrics

Yoke Hwee and Ng Kee Chong

Liew Woei Kang, Mona Iancovici Kidon, Chiang Wen Chin, Lim Siok Hoon, Chan

Severe Anaphylactic Reaction to Ibuprofen in a Child With Recurrent Urticaria

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EXPERIENCE & REASON

Severe Anaphylactic Reaction to Ibuprofen in a Child

With Recurrent Urticaria

Liew Woei Kang, MBBS, MRCPCH, FAMS

, Mona Iancovici Kidon, MD

a,b

, Chiang Wen Chin, BMedSci, MBBS, MRCPCH

Lim Siok Hoon, MBBS, MRCPCH

, Chan Yoke Hwee, MBBS, MMed

, Ng Kee Chong, MBBS, MMed

Paediatric Allergy, Immunology and Rheumatology Service,

Children’s Intensive Care Unit, and

Children’s Emergency Department, KK Women’s and Children’s

Hospital, Singapore;

Children’s Health Centre, Clalit Health Services, Rishon LeZion, Israel

The authors have indicated they have no ﬁnancial relationships relevant to this article to disclose.

ABSTRACT

An acute anaphylactic reaction after a conventional antipyretic dose of ibuprofen was diagnosed in a child with

allergic rhinitis, recurrent idiopathic urticaria, and nonimmunologic cross-reactive hypersensitivity to nonsteroidal

antiinﬂammatory drugs and acetaminophen. The patient reported several previous, mild (isolated cutaneous)

hypersensitivity reactions after exposure to acetaminophen or ibuprofen. There was no evidence of an underlying

inﬂammatory disease except as described above. Patients with chronic or recurrent idiopathic urticaria and those

with atopic disease represent groups at increased risk of nonsteroidal antiinﬂammatory drug hypersensitivity. Mild

hypersensitivity reactions to acetaminophen and/or ibuprofen may precede subsequent, more-severe adverse reac-

tions. Risks and beneﬁts of continued use of nonsteroidal antiinﬂammatory drugs in these children should be

carefully considered.

BUPROFEN, A PROPIONIC-ACID derivative nonsteroidal

antiinﬂammatory drug (NSAID), is extensively used

in children for analgesia and fever control. Its mecha-

nism of action is the inhibition of prostaglandin produc-

tion by blocking the cyclooxygenase enzymes known as

COX-1 and COX-2, thus shunting arachidonic-acid me-

tabolism, toward the 5-lipoxigenase pathway, resulting

in increased production and release of cysteinyl leuko-

trienes.

Hypersensitivity reactions to NSAIDs are classiﬁed ac-

cording to clinical reaction patterns

1,2

and divided into 2

major classiﬁcation groups. The ﬁrst group comprises

cross-reactive, most likely COX-inhibitor activity–related

clinical syndromes. These syndromes span the spectrum

from classical “aspirin triad” (aspirin-exacerbated respi-

ratory disease) to isolated urticaria and/or angioedema

reactions, which are more common in adults and chil-

dren with chronic urticaria

but also documented in

otherwise healthy children and adults. The second clas-

siﬁcation group contains drug-speciﬁc, most likely im-

munologically mediated reaction types, from cellular-

dependent delayed type hypersensitivity to classical type

I immunoglobulin E–mediated anaphylaxis.

The true incidence of NSAID-hypersensitivity reac-

tions in children is unknown and most likely shows a

marked variability in genetically distinct populations.

There is, however, a known increased incidence of the

cross-reactive type of reactions in children with allergic

respiratory disease.

4–6

By and large, the most common

manifestations of NSAID hypersensitivity in children are

angioedema and urticaria, but respiratory symptoms

may appear as well.

7,8

Patients with chronic urticaria may have exacerba-

tions of their urticaria symptoms after exposure to

NSAIDs. In fact, in some cases, intolerance to NSAIDs is

reported to precede by years the onset of chronic urti-

caria.

However, most such reactions are conﬁned to

symptoms of facial angioedema and urticaria exacerba-

tion, and most children with chronic urticaria can toler-

ate recommended doses of acetaminophen safely.

Here we report the case of a young Nepalese boy,

born in Singapore, who presented with a severe anaphy-

lactic reaction after ingestion of ibuprofen.

Key Words: nonsteroidal antiinﬂammatory drugs, acetaminophen, ibuprofen, child,

allergy, chronic urticaria

Abbreviations: NSAID; nonsteroidal antiinﬂammatory drug; COX; cyclooxygenase

www.pediatrics.org/cgi/doi/10.1542/peds.2006-2634

doi:10.1542/peds.2006-2634

Address correspondence to Liew Woei Kang, MBBS, MRCPCH, FAMS, Rheumatology, Immunology

and Allergy Service, Department of Pediatric Medicine, KK Women’s and Children’s Hospital, 100

Bukit Timah Rd, Singapore 229899. E-mail: liew.woei.kang@kkh.com.sg

American Academy of Pediatrics

e742 LIEW et al

by guest on June 3, 2013pediatrics.aappublications.orgDownloaded from

CASE REPORT

A Nepalese boy who was born in Singapore presented at

12 years of age. He had had a signiﬁcant history of

recurrent urticaria/angioedema since the age of 5 years,

with a frequency of urticaria/angioedema bouts of once

or twice per month. The episodes were mostly unpro-

voked, but some reported triggers included egg inges-

tion, exercise, and acetaminophen ingestion. The patient

has previously taken egg and acetaminophen with no

apparent problems before the onset of these episodes.

With regards to the adverse drug reactions, there

were encounters with acetaminophen on 3 separate oc-

casions at 6, 8, and 12 years of age, with worsening of

urticaria/angioedema symptoms approximately 1 hour

postingestion of paracetamol. The child had also taken

ibuprofen on a few occasions with similar but more-

severe bilateral periorbital angioedema approximately 1

hour after ingestion.

In addition, the patient had had mild-persistent aller-

gic rhinitis since 2 years of age and was treated with

intermittent courses of nasal steroids. There was no his-

tory of previous bronchitis or wheezing episodes, and

there was no signiﬁcant family history of allergic or

autoimmune disease or drug hypersensitivity.

Our patient presented to the KK Women’s and Chil-

dren’s Hospital emergency department with fever and

cough of 1 day’s duration after receiving a 150-mg dose

of ibuprofen (5 mg/kg) from his family physician. He

developed a generalized rash, facial angioedema, and

shortness of breath 1 hour after the ingestion.

The patient was noted to be tachypneic on presenta-

tion, with a respiratory rate of 54 breaths minute and an

oxygen saturation of 89%. He was also noted to be

bradycardic (heart rate from 40 to 60 beats per minute)

and hypotensive (blood pressure trough of 60/40

mm Hg). Other physical ﬁndings included generalized

urticaria and bilateral periorbital and perioral angio-

edema.

Resuscitation was commenced immediately, and his

vital signs stabilized after intravenous adrenaline, hydro-

cortisone, ﬂuid boluses, nebulized salbutamol, and sup-

plemental oxygen. He was subsequently transferred to

our children’s ICU for additional management.

The patient’s subsequent progress was uneventful,

with no further progression or recurrence of symptoms.

The investigations performed included a full septic

workup, which was unremarkable. The results of inves-

tigations for chronic urticaria, including measuring the

erythrocyte sedimentation rate, running renal- and liv-

er-function tests, obtaining complement component 3

and 4 levels, performing mycoplasma serology, and

measuring levels of autoimmune antibodies, were nor-

mal. Results of an examination of a stool sample for ova,

cysts, and parasites were negative. His total immuno-

globulin E level was elevated at 1140 IU/L.

A skin-prick test (SPT) to food allergens, aeroaller-

gens, and ibuprofen was performed in our outpatient

clinic. The syrup ibuprofen solution consumed by the

patient was used in the SPT. We diluted 1 mL of the

syrup solution with 9 mL of normal saline 0.9% before

application to the skin. The patient had positive SPT

reactions to house dust mites (Der P and Der F mix, and

Blomia tropicalis) and cockroach mix. Results of the ibu-

profen SPT were negative, and results of the pulmonary-

function tests were normal.

An acute anaphylactic reaction to ibuprofen was di-

agnosed in this child with nonimmunologic cross-reac-

tive hypersensitivity to NSAIDs and acetaminophen. An

oral provocation test with a selective COX-2 inhibitor is

currently being considered.

DISCUSSION

Here we have described a case of severe anaphylactic

reaction to ibuprofen in a Nepalese boy with recurrent

urticaria and angioedema, persistent allergic rhinitis, and

previous mild hypersensitivity reactions to acetamino-

phen and ibuprofen.

Acetaminophen, the most ubiquitously used antipy-

retic medication for children worldwide, has no signiﬁ-

cant action on peripheral COX-1 and COX-2, but its

antipyretic effect is consistent with a central nervous

system–mediated activity on relatively recently discov-

ered COX-3, found only in the brain and spinal cord.

Thus, although acetaminophen has almost no antiin-

ﬂammatory effects even at high doses and, therefore, is

not an NSAID, strictly speaking, it is an inhibitor of

prostaglandin synthesis, similar to aspirin and the

NSAIDs.

Our patient presented with a severe anaphylactic re-

action including hypotension, respiratory distress, and

cutaneous symptoms and required signiﬁcant resuscita-

tion at the emergency department after a conventional

antipyretic dose of ibuprofen (5 mg/kg). This occurred in

the background of previously mild (isolated cutaneous)

but progressively more severe hypersensitivity reactions

to acetaminophen and ibuprofen. The drug-hypersensi-

tivity reactions developed after the onset of allergic rhi-

nitis and recurrent urticaria in our patient. Although

atopy is not considered a risk factor for most drug allergic

reactions, NSAID hypersensitivity seems to be directly

related to atopy and allergic disease.

An underlying autoimmune disease may be an addi-

tional risk factor. A severe anaphylactoid reaction with

ibuprofen has been reported as the ﬁrst manifestation of

systemic lupus erythematosus in adolescence.

Our pa-

tient has a history of recurrent idiopathic urticaria that

may also be secondary to an as-yet-undiagnosed auto-

immune mechanism. Therefore, patients who present

with such severe reactions to NSAIDs may need an

evaluation for an autoimmune inﬂammatory disease.

A cross-reactive hypersensitivity reaction to NSAIDs

and acetaminophen is the likely explanation for our

PEDIATRICS Volume 120, Number 3, September 2007 e743

by guest on June 3, 2013pediatrics.aappublications.orgDownloaded from

patient. We have noted that NSAID cross-reactive hy-

persensitivity reactions are more common than previ-

ously reported, especially in Asian children who present

with facial angioedema and urticaria.

4,7

In addition, we

have observed that the majority of these children under

6 years of age with NSAID hypersensitivity have cross-

reactive hypersensitivity reactions to paracetamol.

We postulate that there may be increased susceptibil-

ity to prostaglandin inhibition in this population, and

genetic markers could possibly be identiﬁed and serve to

abrogate the need for diagnostic oral provocation tests in

the future. Selective COX-2–speciﬁc medications may be

appropriate alternatives for some of the older children.

CONCLUSIONS

There are many facets to NSAID hypersensitivity, and

patients with chronic or recurrent idiopathic urticaria

and those with atopic disease represent groups with

increased risk. Mild hypersensitivity reactions to acet-

aminophen and/or ibuprofen may precede subsequent,

more-severe adverse reactions. Continued use of

NSAIDs in patients with previous hypersensitive reac-

tions may result in increasingly severe responses includ-

ing systemic anaphylactoid reactions.

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DOI: 10.1542/peds.2006-2634

2007;120;e742Pediatrics

Yoke Hwee and Ng Kee Chong

Liew Woei Kang, Mona Iancovici Kidon, Chiang Wen Chin, Lim Siok Hoon, Chan

Severe Anaphylactic Reaction to Ibuprofen in a Child With Recurrent Urticaria

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Full-text available

Nov 2002

Two cyclooxygenase isozymes, COX-1 and -2, are known to catalyze the rate-limiting step of prostaglandin synthesis and are the targets of nonsteroidal antiinflammatory drugs. Here we describe a third distinct COX isozyme, COX-3, as well as two smaller COX-1-derived proteins (partial COX-1 or PCOX-1 proteins). COX-3 and one of the PCOX-1 proteins (PCOX-1a) are made from the COX-1 gene but retain intron 1 in their mRNAs. PCOX-1 proteins additionally contain an in-frame deletion of exons 5-8 of the COX-1 mRNA. COX-3 and PCOX mRNAs are expressed in canine cerebral cortex and in lesser amounts in other tissues analyzed. In human, COX-3 mRNA is expressed as an approximately 5.2-kb transcript and is most abundant in cerebral cortex and heart. Intron 1 is conserved in length and in sequence in mammalian COX-1 genes. This intron contains an ORF that introduces an insertion of 30-34 aa, depending on the mammalian species, into the hydrophobic signal peptide that directs COX-1 into the lumen of the endoplasmic reticulum and nuclear envelope. COX-3 and PCOX-1a are expressed efficiently in insect cells as membrane-bound proteins. The signal peptide is not cleaved from either protein and both proteins are glycosylated. COX-3, but not PCOX-1a, possesses glycosylation-dependent cyclooxygenase activity. Comparison of canine COX-3 activity with murine COX-1 and -2 demonstrates that this enzyme is selectively inhibited by analgesic/antipyretic drugs such as acetaminophen, phenacetin, antipyrine, and dipyrone, and is potently inhibited by some nonsteroidal antiinflammatory drugs. Thus, inhibition of COX-3 could represent a primary central mechanism by which these drugs decrease pain and possibly fever.

Adverse drug reactions in Singaporean children

Article

Full-text available

Jan 2005

Allergic reactions to drugs are considered rare in the paediatric population. Host genetic and environmental factors influence the reported incidence and characteristics of adverse drug reactions (ADRs), and cause significant variation according to the population described and case definition used. We aimed to define the prevalence and characteristics of reported drug allergies in hospitalised children in Singapore. A retrospective case control study was performed through the hospital's inpatient electronic medical record (EMR) for the period of August 2002 to December 2002. The EMR was used to identify children with a previously reported ADR. The control group was randomly selected from patients hospitalised during the same period. Of the 8437 patients hospitalised during the study period, reports of previous ADRs were found in the records of 222 patients. The mean age of the patients was 7.4 years, range 2 months to 17 years (95 percent confidence interval [CI] 6.3 - 8.4). There were 146 males and 160 Chinese. The most commonly-involved medications were betalactam antibiotics (45 percent) and non steroidal anti-inflammatory drug (18.5 percent). Compared to the control group, children with a reported ADR were more likely to be older, with a mean age of 7.4 years versus 4.6 years (p-value less than 0.001), male (odds ratio [OR] 1.7, 95 percent CI 1.2-2.4), of Chinese descent (OR 1.8, 95 percent CI 1.5-5), have an associated chronic illness (OR 3.5, 95 percent CI 2.5-5), and a diagnosis of asthma (OR 2.7, 95 percent CI 1.7-4.5). In our paediatric inpatient population, the risk of reported ADRs increases with age, male gender, Chinese descent and the presence of chronic disease. The major drugs involved are betalactam antibiotics and non-steroidal anti inflammatory drugs.

Early Presentation With Angioedema and Urticaria in Cross-reactive Hypersensitivity to Nonsteroidal Antiinflammatory Drugs Among Young, Asian, Atopic Children

Article

Full-text available

Dec 2005
Pediatrics

Nonsteroidal antiinflammatory drugs (NSAIDs), mainly ibuprofen, are used extensively among children as analgesic and antipyretic agents. Our initial survey in the Kendang Kerbau Children's Hospital in Singapore showed NSAIDs to be the second most common adverse drug reaction-causing medications among children of Asian descent. We attempted to characterize the clinical and epidemiologic profile of NSAID reactions in this group of patients. A retrospective case series from a hospital-based pediatric drug allergy clinic was studied. A diagnosis of NSAID hypersensitivity was made with a modified oral provocation test. Atopy was evaluated clinically and tested with a standard panel of skin-prick tests. We excluded from analysis patients with any unprovoked episodes of urticaria and/or angioedema, patients < 1 year of age, and patients who refused a diagnostic challenge test. Between March 1, 2003, and February 28, 2004, 24 patients, including 14 male patients (58%) and 18 Chinese patients (75%), with a mean age of 7.4 years (range: 1.4-14.4 years), were diagnosed as having cross-reactive NSAID hypersensitivity. A family history consistent with NSAID hypersensitivity was elicited for 17% of patients. None of the patients reported any episodes of angioedema/urticaria unrelated to NSAIDs. The median cumulative reaction-eliciting dose was 7.1 mg/kg. Facial angioedema developed for all patients (100%) and generalized urticaria for 38% of challenged patients, irrespective of age. There was no circulatory compromise, but respiratory symptoms of tachypnea, wheezing, and/or cough were documented for 42% of patients. A cross-reactive hypersensitivity response to acetaminophen was documented for 46% of our patients through their history and for 25% through diagnostic challenge. Compared with patients with suspected adverse drug reactions to antibiotics, patients in the NSAID group were older (7.4 vs 4.8 years) and more likely to have a diagnosis of asthma (odds ratio: 7.5; 95% confidence interval: 3.1-19). Early presentations of facial angioedema and urticaria are key features of dose- and potency-dependent, cross-reactive reactions to NSAIDs in a subpopulation of young, Asian, atopic children. Significant overlap with acetaminophen hypersensitivity, especially among very young patients, for whom the use of a cyclooxygenase-2-specific medication may not be feasible, severely limits options for medical antipyretic treatment.

COX-3, a cyclooxygenase-1 variant inhibited by acetaminophen and other analgesic drugs: Cloning, structure and expression

Article

Jan 2002

Adverse Reactions to Aspirin and Related Drugs

Article

Mar 1981
ARCH INTERN MED

Guy A. Settipane

The term "aspirin intolerance" is defined as acute urticaria-angioedema, bronchospasm, severe rhinitis, or shock occurring within three hours of aspirin ingestion. Aspirin intolerance occurs most commonly in patients with chronic urticaria (23%), in whom it is mostly manifested by the urticaria type of aspirin tolerance, and in asthmatic individuals (4%), in whom it is mostly manifested by the bronchospastic type. There is no definite evidence that aspirin intolerance is mediated by an immunologic reaction. In the bronchospastic type, an association between prostaglandins and the slow-reacting substance of anaphylaxis (SRS-A) seems likely. It is possible that aspirin causes a preponderance of prostaglandin F2 alpha (PGF2 alpha), resulting in bronchospasm. The effect of aspirin on blood histamine is controversial. The two major types of aspirin intolerance seem to be mediated by different mechanisms.

Atopy is a risk factor for nonsteroidal anti-inflammatory drug sensitivity

Article

Feb 2000
ANN ALLERG ASTHMA IM

There is scarce information in the literature about a possible association between atopy and certain clinical manifestations of NSAID sensitivity. (1) To evaluate the prevalence of atopy in patients proved to be sensitive to cyclooxygenase inhibitors. (2) To assess cross-reactivity to two alternative NSAIDs, paracetamol (acetaminophen) and nimesulide. NSAID-sensitive patients attending an allergy clinic and unselected controls were prick tested with inhalant allergens. Oral challenges with NSAIDs were carried out by the single-blinded (SBOC) method. Clinical data about personal and family history of allergic and atopic diseases were obtained by a careful review of the medical records and by direct questioning by experienced allergists. Fifty patients had positive SBOCs to the suspected NSAID and only these were studied. A personal history of atopic diseases was present in 41 patients (82%) and 7 controls (14.5%), and a family history in 24 patients (48%) and 6 controls (12.5%). Prick skin tests with aeroallergens were positive in 39 of 45 patients tested (86.6%) and in 14 of 48 controls (29.1%), (P = .0001). Skin test positivity rates were higher in patients with cutaneous challenge reactions who responded to only one NSAID (single reactors) in comparison to cross-reactors (P = .04). The most frequent clinical manifestations of NSAID sensitivity were (1) cutaneous (angioedema, urticaria) in 34 patients, (2) blended (cutaneous plus respiratory) in 12, (3) respiratory in 3, and (4) anaphylactoid in 1. Aspirin, pyrazolone, paracetamol, and ibuprofen were the drugs more frequently implicated in these reactions. Cross-sensitivity with paracetamol and nimesulide were 32% and 25%, respectively. The prevalence of atopy is increased in challenge-proven NSAID-intolerant patients. The atopic condition may represent an important risk factor for developing reactions to these drugs. Paracetamol and nimesulide are relatively safe alternative choices in those patients, although their use still carries some risk of unwanted reactions.

NSAID facial angioedema in a selected pediatric atopic population

Article

Sep 2000
J INVEST ALLERG CLIN

Epidemiological data for drug reactions in pediatric medical literature as well as in specialized periodicals are scarce. A relationship between nonsteroidal antiinflammatory drugs (NSAIDs), facial angioedema and atopic status has been described in adults. A 10-year retrospective random review of 1,007 charts of atopic children (60.9% male) attending an allergy clinic for management of asthma and/or rhinitis was carried out. Careful attention was given to the written history of NSAID facial angioedema reactions (41 out of 1007, 4.07%) and atopy was confirmed if the patient had a family history and at least one positive skin prick test (>3 mm wheal compared to glycerosaline control) to aeroallergens. Telephone recall was performed when available. Patients were classified into four age groups as follows: a) 0-5 years old; b) 6-10 years old; c) 11-15 years old; and d) 16-21 years old. NSAID facial angioedema rates were as follows: group a 10/493 (2.0%), group b 14/361 (3.8%), group c 10/121 (8.2%), and group d 7/32 (21.8%). Aspirin was the most commonly reported NSAID, and less common were pyrazolones and ibuprofen. Of the 41 patient with chart-reported reactions, 27 (66%) could be contacted by telephone. Of these, 17 patients confirmed the facial angioedema NSAID reaction occurring once or more due to inadvertent exposure. No reactions were reported in the remaining 10 patients since no other NSAID, except acetaminophen, had been used for fever or pain. In conclusion, our data show the age dependency of these reactions and its rather frequent occurrence in such selected pediatric atopic populations. Since NSAIDs are used more frequently in younger children, exposure would not be a plausible explanation for these observations.

Sensitivity to nonsteroidal anti-inflammatory drugs

Article

Jan 2003
ANN ALLERG ASTHMA IM

Aspirin can provoke reactions ranging from respiratory to cutaneous in susceptible individuals. There has been particular attention looking at the role of cyclo-oxygenase enzymes 1 and 2 and their role in aspirin-exacerbated respiratory disease. Patients who present with a spectrum of allergic and pseudoallergic reactions to aspirin pose a special challenge for the physician. This article discusses proposed classification system, clinical manifestations, pathogenesis of disease, and current treatment options of aspirin-related disease. Relevant articles in the medical literature were derived from searching the MEDLINE database with key terms aspirin-sensitive asthma, cyclo-oxygenase enzymes 1 and 2. Sources also include review articles, randomized control trials, and standard textbooks of allergy and immunology. Aspirin-exacerbated respiratory disease remains a complex, heterogenous disease with varied clinical presentations. There have been many advances in trying to elucidate the pathogenesis of this disease. The classification system presented will provide greater ease when reading the literature and communicating with one another. Oral aspirin challenge remains the diagnostic test of choice for both respiratory and cutaneous reactions. Aspirin desensitization is an option for those with refractory respiratory disease or who require aspirin for other medical conditions. This review discusses the challenges in classification, diagnosis, and treatment of those patients with a sensitivity to aspirin. Special attention is made to the possible mechanisms mediating disease progression and how specific therapies, such as leukotriene modifiers, may be helpful.

Intolerance to nonsteroidal anti-inflammatory drugs might precede by years the onset of chronic urticaria

Article

May 2003
J ALLERGY CLIN IMMUN

Riccardo Asero

Recent studies have found that most otherwise normal subjects with a history of acute urticaria induced by several nonsteroidal anti-inflammatory drugs (NSAIDs) show a wheal-and-flare reaction on intradermal injection of autologous serum. This phenomenon has been previously observed in patients with chronic urticaria (CU) and suggests a possible common background in CU and NSAID-induced urticaria. A relationship between these 2 conditions is further suggested by the fact that up to 30% of patients with CU have a worsening of their skin disorders after the ingestion of chemically unrelated NSAIDs. I sought to assess whether otherwise normal subjects with multiple or single NSAID intolerance show a propensity to have CU. Two hundred eighty otherwise normal patients with an unequivocal history of acute urticaria induced by NSAIDs seen during the last 10 years were studied. On the basis of both clinical history and oral challenge tests with at least 2 alternative NSAIDs, the patients were classified as having single or multiple NSAID intolerance. All the patients were re-evaluated within the end of 2002, 1 to 10 years after the first visit, to assess the onset of CU. One hundred allergic adults without a history of CU and of drug allergy followed up for 1 to 10 years were used as control subjects. One hundred fifty-nine and 121 patients were finally considered as having single or multiple NSAID intolerance, respectively. At the follow-up visit, 93 (33%) of 280 patients had CU. The prevalence of CU was very similar in subjects with single or multiple NSAID intolerance (48/159 [30%] vs 45/121 [37%], respectively; P = not significant). Only 1 (1%) of 100 atopic control subjects had CU during the follow-up period (P <.001). Among single NSAID reactors, patients who had CU had a significantly higher prevalence of intolerance to aspirin than those who did not have CU (36/48 [75%] vs 41/111 [37%], P <.001), whereas the latter had a markedly higher prevalence of intolerance to pyrazolone drugs (52/111 [47%] vs 10/48 [21%], P <.01). Altogether, only 12 (15%) of 82 patients intolerant to drugs other than aspirin versus 36 (47%) of 77 aspirin reactors had CU (P <.001). NSAID intolerance might precede the onset of CU by years. Both multiple and single NSAID reactors with a history of aspirin-induced urticaria seem at higher risk for CU than patients with a history of single intolerance to NSAIDs other than aspirin.

Hypersensitivity to non-steroidal anti-inflammatory drugs in childhood

Article

Sep 2004

Although largely investigated in adults, the issue of hypersensitivity to non-steroidal anti-inflammatory drugs (NSAIDs) in childhood is unsettled due to lack of sufficient data. The purpose of this study is to examine the clinical syndromes of hypersensitivity to NSAIDs in children and adolescents. We performed a review of relevant papers on cutaneous and respiratory adverse reactions triggered by NSAIDs in pediatric patients, and a recount of our own experience in 43 well-characterized NSAID-sensitive children with cutaneous reactions who were submitted to controlled oral challenges with NSAIDs and the new inhibitors of the enzyme isoform cyclooxygenase-2 (COX-2). Although it has been suggested that allergic and pseudoallergic reactions to NSAIDs in children occur rarely, their prevalence remains largely unknown due to the scarcity of studies. About 23% of NSAID-sensitive patients seen in our institutions are young patients aged 8-18 yr who more frequently develop facial angioedema as their main clinical manifestation. Most patients are atopic and show reactions to more than one drug (cross-reactors). Drugs that inhibit COX-2 with higher specificity than classic NSAIDs are better tolerated in young NSAID-hypersensitive patients.

Severe Anaphylactic Reaction to Ibuprofen in a Child With Recurrent Urticaria

Abstract

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