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Allergic and nonallergic hypersensitivity reactions to silicone: A report of one case

Allergic and nonallergic
hypersensitivity reactions to
silicone: a report of one case
A. Rubio*, C. Ponvert, O. Goulet, P. Scheinmann, J. de
Keywords: children; immediate-type allergy;
prick-tests; silicone.
Although silicones were presumed to be
inert materials, immune-mediated reac-
tions in human and animal tissues have
been reported
since the begin-
ning of the use of
silicone implants
(1–5). Silicone
has been impli-
cated as the
causative agent
of chronic local or systemic reactions
such as inflammatory processes,
foreign-body reactions or rheumatologic
diseases. However, at present, only one
case of immediate-type hypersensitivity
to silicone has been reported (5). We
report a case of immediate pruritus,
oedema and erythema upon the first
insertion of a silicone nasogastric tube in a
10-year-old boy.
A 10-year-old nonatopic boy was
treated with enteral nutrition through a
polyurethane nasogastric tube for a
severe Crohn!s disease without incident
during several weeks. For greater com-
fort considering the more flexible con-
sistency of silicone, it was suggested
that the patient try a silicone nasogas-
tric tube. The tube was inserted without
any resistance. However, a few minutes
later, the patient experienced nasal and
throat pruritus, erythema and mild
oedema of the wings of nose and
mouth, and repeated sneezing. The tube
was immediately withdrawn. Symptoms
rapidly decreased and totally disap-
peared within 2 h without requiring
medication. A polyurethane nasogastric
tube was reinserted and nutrition was
resumed uneventfully. No allergological
work-up was performed at the time of
the reaction. Two years later, the
insertion of a central venous catheter
for parental nutrition was required.
During the preanaesthesia consultation,
the allergic-like event was recalled by
the parents. A work-up for suspected
latex and/or silicone allergy was under-
taken. Latex serum IgE determination
was negative, as well as skin prick tests
with latex extracts and with a silicone
gel (Silisonde
, Vygon, Ecouen,
France). Prick tests with silicone were
also negative in three control subjects
with no suggestive history of silicone
allergy. Negative and positive (codeine
phosphate) prick test controls (Staller-
`nes, Antony, France) elicited negative
and positive responses respectively.
Challenge tests (prolonged cutaneous
and mucous contact with a silicone
nipple and with a silicone nasogastric
tube) were negative. The central venous
catheter was inserted in the internal
jugular vein and was well tolerated on
the short and long term.
Medical silicone devices have the
potential to induce foreign-body and
local and systemic nonspecific
(nonallergic) inflammatory reactions.
However, evidence for true allergic
reactions to silicone in implants and
silicone-coated medical devices has
also been provided (1–6). Delayed
hypersensitivity seems to play a major
role in the de novo development of this
allergy (4).
In our patient, the rapid course of
events suggested a type-I hypersensitiv-
ity reaction. At present, only one case
of immediate-type hypersensitivity to a
silicone tracheal tube has been
reported by Stuck et al. (5). Skin
prick and patch tests and specific-IgE
were negative, and only scratch tests
with native tube material generated
positive responses. Unfortunately, our
patient was tested 2 years after the
initial episode. Specific-IgE and prick
test with latex and prick test with
silicone were negative, and the child
tolerated prolonged cutaneous,
mucous and venous contact with
silicone. We cannot explain the initial
reaction of the child to the insertion of
a silicone nasogastric tube. Neverthe-
less, it is probable that this outcome
reflects an initial nonspecific (nonaller-
gic) reaction to the silicone tube rather
than a true IgE-mediated hypersensitiv-
ity spontaneously resolving within
2 years.
We report the case of a child with
suspected immediate-type allergy to
latex and/or silicone. Together with
the data of the literature, our
observation confirms that most
reactions to silicone are nonallergic
(nonspecific) and suggests that the
specificity and negative predictive value
of immediate-reading skin tests with
silicone are good.
´de Nice Sophia Antipolis
Poˆ le Enfant Adolescent, CHU de Nice
Hoˆ pital Archet 2
133 Route de Saint Antoine de Ginestie
06200 Nice (France)
Tel.: 00 33 (0)4 92 03 64 71
Fax: 00 33 (0)4 92 03 59 51
Accepted for publication 16 March 2009
Allergy 2009: 64:1555
"2009 John Wiley & Sons A/S
DOI: 10.1111/j.1398-9995.2009.02086.x
1. Hunsaker DH, Martin PJ. Allergic
reaction to solid silicone implant
in medial thyroplasty. Otolaryngol
Head Neck Surg 1995;113:
2. Smalley DL, Shanklin DR. T-cell-specific
response to silicone gel. Plast Reconstr Surg
3. Heggers JP, Kossovsky N, Parsons RW,
Robson MC, Pelley RP, Raine TJ.
Biocompatibility of silicone
implants. Ann Plast Surg 1983;
4. Goldblum RM, Pelley RP, O!Donell AA,
Pyron D, Heggers JP. Antibodies
to silicone elastomers and
reactions to ventriculoperitoneal
shunts. Lancet 1992;340:
5. Stuck BA, Hecksteden K, Klimek L,
¨rmann K. Type I hypersensitivity to a
silicone tube after laryngectomy. HNO
6. Kossovsky N, Heggers JP, Robson MC.
Experimental demonstration of the
immunogenicity of silicone-protein
complexes. J Biomed Mater Res
We report the case of a
child with suspected
immediate-type allergy
to latex and/or silicone.
"2009 John Wiley & Sons A/S Allergy 2009: 64: 1554–1561 1555
... Although rare, hypersensitivity-like reactions to silicone have been described before. [16][17][18][19][20][21][22] Platinum, ranging in a dose from 0.1 to 10 mg per two implants, is used as a catalyst in the hydrosilylation reaction for the crosslinking of silicone elastomers. 23 A single silicone gel-filled breast implant contains an estimate of 7-14 μg per kg platinum, whereas a saline-filled breast implant contains a platinum level ranging from below detection limit up to 3 μg per kg. ...
It has been suggested that compounds present in silicone breast implants (eg, silicone particles or heavy metals such as platinum) migrate into the body and can cause systemic symptoms in susceptible women, causing what is known as breast implant illness. This pilot study investigates possible associations between hair platinum levels in patients with breast implants and breast implant illness, and evaluates its possible use for diagnostic purposes. Methods: Patients were included from the silicone outpatient clinic at Amsterdam University Medical Centre. Platinum concentration in hair samples of 10 women with breast implants and systemic symptoms (group A) was compared with that in 10 women with breast implants but no symptoms (group B), and a control group of 10 women without implants or symptoms (group C), using laser ablation inductively coupled plasma mass spectrometry. Radiological imaging was used to assess implant ruptures or silicone leakage. Results: A median platinum concentration of 0.09 μg per kg [IQR 0.04-0.15] was found in group A, 0.08 μg per kg [IQR 0.04-0.12] in group B, and 0.04 μg per kg [IQR 0.02-0.13] in group C, with no statistical significant difference between the groups (Kruskal-Wallis test, P = 0.43). No correlation between radiologically proven implant leakage and platinum level was found. Conclusions: There was no statistically significant difference in hair platinum levels in women with or without silicone breast implants or breast implant illness. Therefore, based on this pilot study, we do not recommend this test for clinical use. Given the small sample size, more research is required to fully assess its possible use for diagnostic purposes.
... Silicone can be acceded to as a sensitizer [54][55][56][57][58][59][60]. There may be some debate as to whether any silicone-related reaction is always an acquired entity or whether some may have crossreactive or direct immune reactions that are stimulated after non-specific polyclonal activation for other reasons. ...
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Non-clonal mast cell activation disorder (syndrome) (NC-MCAD) and autoimmune/inflammatory syndrome induced by adjuvants (ASIA) are complex syndromic and spectral clinical entities which have contemporaneously garnered considerable attention and rightfully so. NC-MCAD presents with a predominantly allergic profile, and causative clinical variables may or may not be identified. Manifest NC-MCAD illnesses can be complex and involve several organ systems. Such diversity may be in part explained by the ubiquity and plasticity of the mast cell. ASIA, due to its broad definition, continues to expand as a clinical entity, especially with the greater recognition of what might constitute adjuvancy. Such diversity has the potential to overly stretch the boundaries for scientific investigation. For both NC-MCAD and ASIA, the inciting molecular mechanisms require elucidation. Future research would benefit from greater precision for clinical diagnosis and risk factor identification, and the latter would be potentially facilitated by the discovery of reliable laboratory markers. Some patients with ASIA may present with clinical features that may be identified as NC-MCAD. This review examines the potential spectral nexus of NC-MCAD and ASIA and considers the role of the mast cell in such a possible interface.
... Hypersensitivity reactions to shunts are rare. Although silicone is considered as an inert biomaterial, it has been implicated to cause chronic local or systemic reactions which include inflammatory processes, foreign body reactions, and autoimmune reactions [5]. ...
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Silicone allergy in patients with ventricular shunts is uncommon hence easily missed. However, there are clinical features that could assist in identifying and diagnosing this condition. We discuss a case where a patient with a ventriculoperitoneal (VP) shunt presented to us with features suggestive of silicone allergy.
... Reactions include allergic contact dermatitis, granuloma formation, systemic sclerosis, and a psoriasiform eruption, among others [75][76][77][78]. Rates of sensitization to silicone and silicone polymers are increasing in both topical and implanted exposures [79][80][81]. ...
... When silicon was incubated with human monocytes, elevated levels of inflammatory cytokines including IL-1 beta, IL-6 and TNF-alpha were noted [50]. Furthermore, a local lymph node assay in mice showed weak to moderate skin sensitization potential in four out of five silicon materials tested for skin sensitization [51,52]. The melting point of dimethicone is generally below 50°C depending on which polymer is used. ...
Full-text available
Irritant contact dermatitis is an extremely common condition resulting from epidermal exposure to any number of skin irritants. Upon contact with skin irritants, the epidermis develops many identifiable problems including specific epidermal lipid deficiencies, elevated epidermal pH with concomitant suppression of epidermal lipid production, pH-dependent susceptibility to infection, inflammation, and aberrant calcium gradients. By addressing these problems simultaneously, and through irritant avoidance, the treatment of irritant contact dermatitis can be maximized.
... Incubation of human monocytes demonstrated elevated levels of inflammatory cytokines including IL-1β, IL-6, and TNF-α [51]. Furthermore, local lymph node assay in mice showed weak to moderate skin sensitization potential in four out of five silicon materials tested for skin sensitization [52,53]. ...
Irritant contact dermatitis (ICD) is a commonly occurring non-specific cutaneous inflammatory response to topical chemical, physiologic, and biologic toxins. Direct damage to the skin induces barrier dysfunction, epidermal cell stimulation, and pro-inflammatory mediator release leading to a visibly variable, itchy cutaneous reaction. Workplace exposure of the hands to water, cleansers, and solvents remains the most common source of ICD. There is no diagnostic test for ICD, as such a diagnosis is based on history and clinical findings. Exclusion of allergic contact dermatitis, atopic dermatitis, and other xerotic conditions is a key part of the work-up. Prevention and treatment of ICD lies in the utilization of barrier protectants, incorporation of hydrating cleansers to decrease disruption of the barrier, and avoidance protocols and protective gear (fabrics, gloves, etc.). Therapeutic tools to treat ICD include acute anti-pruritic and antibacterial soaks, cutaneous barrier protectants such as petrolatum, paraffin, and dimethicone; lipid-laden moisturizers rich in wool wax alcohols, ceramides, and cholesterol esters and colloidal oatmeal based creams; and, when there is an eczematous component, the restrained use of anti-inflammatory agents such as topical corticosteroids may be warranted. Future research in ICD pathophysiology will yield more precise treatment options for future patients and clinicians.
... 30 However, recent case reports have described allergy-like reactions in patients with silicone in pacemakers, nasogastric tubes and cochlear implants. [31][32][33] More recently, Hajdu et al. 34 suggested that systemic symptoms following exposure to silicone, such as described in ASIA, may only appear in subjects with underlying diseases or high susceptibility. In addition, a study in 2008 demonstrated that women with silicone breast implants had a higher serum IgE than women without silicone breast implants. ...
Background: Since their introduction, the safety of silicone breast implants has been under debate. Although an association with systemic diseases was never established, women continuously blamed implants for their unexplained systemic symptoms. In 2011, a pattern of symptoms caused by systemic reactions to adjuvants (e.g. vaccines, silicone) was identified: 'autoimmune syndrome induced by adjuvants' (ASIA). Our aim was to collect a cohort of women with silicone breast implants and unexplained systemic symptoms to identify a possible pattern and compare this with ASIA. Methods: Women with silicone breast implants and unexplained systemic symptoms were invited through national media to visit a special outpatient clinic in Amsterdam. All were examined by experienced consultant physicians and interviewed. Chest X-ray and laboratory tests were performed. Results: Between March 2012 and 2013, 80 women were included, of which 75% reported pre-existent allergies. After a symptom-free period of years, a pattern of systemic symptoms developed, which included fatique, neurasthenia, myalgia, arthralgia and morning stiffness in more than 65% of women. All had at least two major ASIA criteria and 79% fulfilled ≥ 3 typical clinical ASIA manifestations. After explantation, 36 out of 52 women experienced a significant reduction of symptoms. Conclusions: After excluding alternative explanations, a clear pattern of signs and symptoms was recognised. Most women had pre-existent allergies, suggesting that intolerance to silicone or other substances in the implants might cause their symptoms. In 69% of women, explantation of implants reduced symptoms. Therefore, physicians should recognise this pattern and consider referring patients for explantation.
A 13-year-old, male Pomeranian dog was presented for scleral rupture with intraocular hemorrhage and retinal detachment in the right eye. After intrascleral silicone ball prosthesis, recurrent swelling and granulomatous blepharitis were observed for 140 d and finally melting keratitis developed. Although an intraorbital prosthesis was implanted, recurrent, serious, erosive, and ulcerative blepharitis developed with high plasma C-reactive protein concentrations. Since the blepharitis could not be controlled, the silicone ball was removed and the affected orbit was debrided. The blepharitis resolved rapidly, and the orbit healed routinely. Positive allergic reactions to silicone were discovered through a patch test. Key clinical message: To the authors' knowledge, this is the first report on silicone allergy in a dog with positive allergic reactions to silicone in the patch test.
Objective: This study investigated the feasibility of obtaining ear impressions for hearing aids by using 3-dimensional high-resolution computed tomography (HRCT) images. Study design: Case series. Setting: One referral tertiary center. Subjects and methods: Hearing-impaired adults who were fitted with 1 or 2 behind-the-ear hearing aid(s) and had undergone temporal bone HRCT for various ear pathologies were enrolled in this study. Earmolds were fabricated from the impressions obtained using the conventional ear canal silicone injection technique and the HRCT reconstructed technique. Outer ear canal resonance frequencies and amplitude in open ears and those measured with silicon and HRCT reconstructed earmolds were determined through real-ear gain measurements, including real-ear unaided gain (REUG) and real-ear occluded gain (REOG), for comparison. Results: A total of 50 HRCT reconstructed earmolds were compared with 50 conventional silicon injection earmolds. The average value of open ear canal resonance amplitude (REUG) for each ear was 0.41 to 16.76 dB. No statistically significant difference in resonance amplitude (REOG) was observed between silicon and reconstructed earmolds (paired t test, P > .05). The mean insertion loss (REOG-REUG) at all frequencies also did not differ significantly between the two earmolds (paired t test, P > .05). Conclusion: According to our real-ear measurements, acoustic characteristics of the HRCT reconstructed earmolds were compatible with those of the silicone injection earmolds. Despite concerns about increased cost and radiation exposure, the HRCT reconstructed technique is a clinically useful and applicable method and can reduce potential safety complications for difficult cases.
Although rare, allergic contact dermatitis (ACD) is well described to various components of electrical cardioversion devices. Silicone is a compound described in cases of ACD, such as pacemakers, breast implants or cochlear implants. The location of the lesions usually assists the identification of the agent. However, differential diagnosis with infectious processes is required. The referral to Immunoallergology’s Department allows an adequate investigation, with epicutaneous contact tests, being able to identify the cause and offer safe alternatives. The authors describe a clinical case of suspected contact allergy to implanted cardioverter‑defibrillator (CRT‑D) components. © 2018, Sociedade Portuguesa de Alergologia e Imunologia Clinica. All Rights Resreved.
When questioned, about 10% of the parents report suspected hypersensitivity to at least one drug in their children. However, only a few of these reactions can be confirmed as allergic after a diagnostic workup. There is still a lack of knowledge on drug hypersensitivity epidemiology, clinical spectrum and appropriate diagnostic methods particularly in children. Meanwhile, the tools used for drug hypersensitivity management in adults are applied also for children. Whereas this appears generally acceptable, some aspects of drug hypersensitivity and management differ with age. Most reactions in children are still attributed to betalactams. Some manifestations, such as non-steroidal anti-inflammatory drug-associated angioedema and serum sickness-like reactions are more frequent among young patients as compared to adults. Risk factors such as viral infections are particularly frequent in children, making the diagnosis challenging. The practicability and validity of skin test and other diagnostic procedures need further assessment in children.This paper presents an up-to-date review on epidemiology, clinical spectrum, diagnostic tools and current management of drug hypersensitivity in children. A new general algorithm for the study of these reactions in children is proposed. Data are presented focusing on reported differences between pediatric and adult patients, also identifying unmet needs to be addressed in further research.This article is protected by copyright. All rights reserved.
Nonsteroidal anti-inflammatory drugs (NSAID) are the second-most frequent drugs that cause hypersensitivity reactions among children. Studies related to NSAIDs hypersensitivity in children are limited. In this study, we aimed to evaluate children admitted with suspicion of NSAIDs reaction. Between January 1, 2011, and November 30, 2014, we included patients with suspicion of NSAIDs hypersensitivity in our clinic. For evaluation, skin tests and oral provocation tests with the drug (suspected or alternative) were proposed. Reactions were classified and defined according to the latest European Academy of Allergy and Clinical Immunology position paper on NSAID hypersensitivity. During the study period, 123 patients (with 136 drug reactions) were admitted to our clinic with suspected NSAID hypersensitivity. The mean (standard deviation) age of the patients, 67 female (55%), was 83.10 ± 56.05 months. Thirteen patients described reactions to more than one chemically unrelated NSAID, and 110 patients described reactions with chemically similar drugs. Eight patients were not included because they did not have provocation tests. Thus, 115 patients were evaluated. A hundred and thirty provocations were performed. Twenty patients (17.4%) were diagnosed with NSAID hypersensitivity (13 patients diagnosed by provocation tests and 7 patients diagnosed according to their history). The most frequently encountered agent was ibuprofen (50% [10/20]). Eighty percent (16 patients) of the reactions were considered "non-cross-reactive type." Fifteen patients (75%) were classified as having single-NSAID-induced urticaria and/or angioedema, three patients were classified as having NSAID-induced urticaria and/or angioedema, one patient was classified as having NSAID-exacerbated respiratory disease, and the other patients were classified as having single-NSAID-induced delayed hypersensitivity reactions. Detailed history and drug provocation tests are important to verify NSAID hypersensitivity. The most common type is the non-cross-reactive type, and, in our study, the most common responsible drug was ibuprofen.
Although non-steroidal anti-inflammatory drug hypersensitivity (NSAID-H) has been widely studied in adults, there is still a lack of data regarding the features and phenotypes of NSAID-H in children. Our aim was to define risk factors and different phenotypes according to clinical patterns. Patients with a history of reaction to any NSAIDs referred between January 2012 and October 2014 were included. After completing a European Network for Drug Allergy (ENDA) questionnaire, initial skin and/or oral provocation tests (OPTs) were performed for the offending drug. Additional OPTs were done with aspirin in case of NSAID-H to determine cross-reactivity. NSAID-hypersensitive patients were defined as being either a selective responder (SR) or cross-intolerant (CI) and further categorized according to either the ENDA/GA2LEN classification or an alternative scheme by Caimmi et al. [Int Arch Allergy Immunol 2012;159:306-312]. Among 121 patients [58.7% male, average age 7.8 years (4.7-10.8)] with 161 NSAID-related reactions, 110 patients with 148 reactions were assessed. NSAID-H was diagnosed in 30 (27%) patients with 37 (25%) reactions. Multivariate regression analysis revealed that an immediate-type reaction and respiratory symptoms during the reaction increased the risk of a reproducible NSAID-related reaction (OR 3.508, 95% CI 1.42-8.7, p = 0.007; OR 3.951, 95% CI 1.33-11.77, p = 0.014, respectively). Additional OPTs revealed 13 SRs and 14 CIs. A family history of allergic disease was more frequent in CIs compared to SRs (57.1 vs. 15.4%, p = 0.031). Reactions belonging to CIs were more frequently characterized by angioedema compared to those of SRs (81.3 vs. 46.2%, p = 0.019). SRs and CIs were further classified as single NSAID-induced urticaria/angioedema and/or anaphylaxis (n = 13), NSAID-induced urticaria/angioedema (n = 7), NSAID-exacerbated cutaneous disease (n = 2) and NSAID-exacerbated respiratory disease (n = 1). Four CIs could not be categorized according to either classification system. One SR could not be categorized according to ENDA/GA2LEN. During childhood, NSAID-H exhibits different phenotypes and the majority of them can be categorized with current classification systems; however, classifications based on adult data may not exactly fit NSAID-H in paediatric patients. © 2015 S. Karger AG, Basel.
Während unspezifische Reizungszustände der Trachea beim Laryngektomierten häufig auftreten, sind allergische Reaktion gegenüber Trachealkanülen oder ihren Bestandteilen bisher lediglich als Kontaktallergie dokumentiert. Hier wird erstmals eine allergische Reaktion vom Soforttyp vorgestellt. Der laryngektomierte Patient verwendete regelmäßig Silikonkanülen zum Schwimmen und berichtete über zunehmende Reizzustände der Luftröhre während und nach deren Verwendung. Es wurde ein Pricktest mit inhalativen Allergenen und ein Epikutantest mit den Testreihen Standard, Gummi, Kleber sowie mit Material aus der Schwimmkanüle durchgeführt. In einer Scratchtestung wurde ebenfalls das native Material getestet. Es erfolgte die Bestimmung von Gesamt-IgE und spezifischem IgE gegen Latexallergene. Der Pricktest sowie sämtliche Epikutantestungen waren negativ. Im Scratchtest fand sich eine deutlich positive Reaktion gegenüber dem Kanülenmaterial. Die positiven Testergebnisse im Hauttest belegen die spezifische Sensibilisierung gegenüber der Schwimmkanüle bzw. ihrer Bestandteile im Sinne einer Soforttypreaktion. Unklar allerdings blieb bis zuletzt das verantwortliche Agens.
Non-opioid analgesics, antipyretics and nonsteroidal anti-inflammatory drugs are widely used, but suspected allergic reactions to these drugs are rare, especially in children. Most frequent reactions are cutaneous (urticaria, angioedema) and respiratory (rhinitis, asthma). Other reactions (anaphylaxis, potentially harmful toxidermias) are rare. In a few patients, reactions may result from a specific (allergic) hypersensitivity, with positive responses in prick and intradermal tests (anaphylaxis, immediate urticaria and/or angioedema) and in intradermal and patch tests (non-immediate reactions). However, most reactions result from a non-specific (non-allergic) hypersensitivity (intolerance), with a frequent cross-reactivity between the various families of analgesics, antipyretics and nonsteroidal anti-inflammatory drugs, including paracetamol. Based on a convincing clinical history and/or positive responses in challenge tests, intolerance to non-opioid analgesics, antipyretics and nonsteroidal anti-inflammatory drugs has been diagnosed in 13 to 50% of the patients with allergic-like reactions to these drugs. Risk factors are a personal atopy and age. Prevention is based on administration of other (families of) analgesics, antipyretics and nonsteroidal anti-inflammatory drugs in patients with allergic hypersensitivity to these drugs. In patients with non-allergic hypersensitivity, prevention is based on administration of drugs with a low cyclo-oxygenase-1 inhibitory activity (if tolerated). Desensitization is efficient in patients with respiratory reactions, but does not work in patients with mucocutaneous reactions and anaphylaxis.
The nonsteroidal anti-inflammatory drugs (NSAIDs) hypersensitivity work-up is based on clinical history, skin tests, and drug provocation tests. The negative predictive value (NPV) of the latter is not established. A cohort study was conducted in the Allergy Department in Montpellier to evaluate the NPV of the provocation test with NSAIDs in patients with clinical presentation suggestive of hypersensitivity, and negatively tested. Patients were contacted at least 6 months after the work-up. Patients who took NSAID and reacted were proposed a new allergy work-up, which included a provocation test with the culprit drug. Among the 393 patients contacted, 279 (71.0%) were followed up. Two hundred and sixty (93.2%) patients had taken a NSAID at least once: 139 (53.5%) the same drug as the one tested and 215 (82.7%) an alternative (94, 33.7% taking both the tested NSAID and an alternative). Eight patients (3.1%) reported a reaction (five with the negatively tested NSAID and three with another NSAID). All the reactions occurred immediately after the first administration and were not severe. Among the five patients who reacted with the negatively tested NSAID, only three accepted a re-challenge, negative in two cases and positive in one, representing a NPV of 97.8% (95% CI: 95.4-100%). Three patients (3/215) reported a reaction when an alternative NSAID was taken, representing a NPV of 98.6% (95% CI: 97-100%). The NPV of NSAIDs drug provocation test is high. This should reassure physicians who might hesitate to prescribe NSAIDs, especially in patients with negative allergic work-ups.
To cite this article: Kowalski ML, Makowska JS, Blanca M, Bavbek S, Bochenek G, Bousquet J, Bousquet P, Celik G, Demoly P, Gomes ER, Niżankowska-Mogilnicka E, Romano A, Sanchez-Borges M, Sanz M, Torres MJ, De Weck A, Szczeklik A, Brockow K. Hypersensitivity to nonsteroidal anti-inflammatory drugs (NSAIDs) – classification, diagnosis and management: Review of the EAACI/ENDA and GA2LEN/HANNA. Allergy 2011; 66: 818–829. Nonsteroidal anti-inflammatory drugs (NSAIDs) are responsible for 21–25% of reported adverse drug events which include immunological and nonimmunological hypersensitivity reactions. This study presents up-to-date information on pathomechanisms, clinical spectrum, diagnostic tools and management of hypersensitivity reactions to NSAIDs. Clinically, NSAID hypersensitivity is particularly manifested by bronchial asthma, rhinosinusitis, anaphylaxis or urticaria and variety of late cutaneous and organ-specific reactions. Diagnosis of hypersensitivity to a NSAID includes understanding of the underlying mechanism and is necessary for prevention and management. A stepwise approach to the diagnosis of hypersensitivity to NSAIDs is proposed, including clinical history, in vitro testing and/or provocation test with a culprit or alternative drug depending on the type of the reaction. The diagnostic process should result in providing the patient with written information both on forbidden and on alternative drugs.
Hypersensitivity to cyclooxygenase (COX) inhibitors is rare in children. We studied 164 children reporting 213 reactions to paracetamol, ibuprofen and/or acetylsalicylic acid (ASA). Most reactions were cutaneous, either isolated or associated with respiratory symptoms and/or anaphylaxis. Based on a convincing clinical history or positive responses in challenges with the drug(s), hypersensitivity to one or several drug(s) was diagnosed in 49.4% of the children (60, 76.5 and 23.2% of the children reporting reactions to ASA, ibuprofen and paracetamol respectively). Cross-reactivity between nonsteroidal anti-inflammatory drugs (NSAIDs) was frequent (69.1%), but only 10.6% of the NSAID-sensitive children reacted to paracetamol. In contrast, all paracetamol-sensitive children reacted to NSAIDs. Anaphylaxis, immediate and accelerated reactions, atopy, older age and chronic/recurrent urticaria were risk factors for hypersensitivity and/or cross-reactivity between ASA, ibuprofen and paracetamol. In conclusion, hypersensitivity to COX inhibitors was frequent, especially in children reporting severe and/or immediate and accelerated reactions, and in older and atopic children. Cross-reactivity was frequent, suggesting that most reactions resulted from a non allergic hypersensitivity linked to the pharmacological properties of the drugs. However, in a few children, the reactions may result from allergic hypersensitivity to selective (families of) drugs, with tolerance to other drugs.
Silicone elastomers used to make medical implants and prostheses are generally believed to be biologically inert. However, we have seen two patients who showed severe, apparently immunemediated, reactions to ventriculoperitoneal (VP) shunts. We used an enzyme-linked immunosorbent assay in which Silastic tubing served as the solid-phase antigen to test serum from the two patients, five other VP shunt patients without inflammatory reactions, and nine healthy adults. IgG binding to Silastic tubing was consistently higher in the two patients than in the healthy or patient controls. The IgG seemed to be binding specifically, since IgG Fab fragments also bound to the tubing, and preincubation of serum with Silastic or silylated proteins removed most of the activity. These findings show that specific immune reactivity to elastomers of polydimethylsiloxane can develop in human beings.