Drug-induced enterocolitis syndrome (DIES) in a 10-year-old girl.

We report the case of a child presenting with an adverse drug reaction highly suggestive of drug-induced enterocolitis syndrome (DIES) to amoxicillin (AMX). A 10-year-old girl developed repetitive vomiting and pallor without cutaneous or respiratory symptoms 2h after AMX intake. DIES is not a well-described entity, and very few data are available in the literature. In the absence of an existing definition, the diagnosis of DIES can only be suspected and is based on its homology with food protein-induced enterocolitis (FPIES). The major criterion is the recurrence of repetitive and often incoercible vomiting occurring within 1-4h of ingestion of the culprit food in the absence of IgE-mediated allergic classic skin and respiratory symptoms. Once the diagnosis of DIES to AMX is suspected, an open challenge with AMX should be undertaken with caution, under medical supervision in a day hospital unit because of the risk of severe recurrence. Once the diagnosis is confirmed, AMX should be contraindicated to avoid severe reactions.

Non-immediate-reading skin tests and prolonged challenges in non-immediate hypersensitivity to beta-lactams in children.

BACKGROUND: A minority of children reporting non-immediate reactions to beta-lactams (BLs) are allergic. Allergy workup usually includes late-reading (48-72 hours) skin tests (ST) and short (1-3 days) drug provocation tests (DPT), regardless of the chronology of the index reaction. The sensitivity of hyper-late-reading (≥6-7 days) ST and of prolonged DPT for the diagnosis of non-immediate hypersensitivity to BLs is yet to be determined. OBJECTIVES: To establish the diagnostic values of late-reading ST and hyper-late-reading ST and of prolonged DPT in children reporting non-immediate reactions to BLs. METHODS: Prospective assessment of children reporting non-immediate reactions to BLs with late- and additional hyper-late-reading intradermal (ID) and patch tests, and if negative, with prolonged DPT. RESULTS: Five hundred and fifty children reporting reactions to a single or several BLs (674 suspected BLs) were included. Non-immediate hypersensitivity to BLs was diagnosed in 63 children (11.5%), reporting 66 reactions (9.8%), based on responses in ST (n = 17, 25.8%: 5 to ID, 8 to patch tests, and 4 to both tests), DPT (n = 43, 65.2%), and clinical history (n = 6, 9.1%), including 3/9 children with severe cutaneous adverse reactions. Skin test positivity was observed after the 6-7th day in 14/17 children, and DPT positivity after a median time of 3 days. No severe reaction was observed after ST or during prolonged DPT. CONCLUSION: Additional hyper-late-reading of ST enhanced their positivity. However, their overall sensitivity remained weak, especially in non-severe cases. Prolonged DPT are safe and may improve the performance of DPT in the diagnosis of non-immediate hypersensitivity to BLs.

[Measles-Mumps-Rubella vaccination of an egg-allergic child sensitized to gelatin]. / Bonne tolérance de la vaccination rougeole-oreillons-rubéole chez un enfant allergique à l'œuf et sensibilisé à la gélatine.

The Measles-Mumps-Rubella (MMR) vaccine is often postponed in egg-allergic patients due to fear of anaphylactic reaction at the time of injection of this vaccin produced on egg derivates. However, this vaccine is recommended by health authorities, especially in case of increased measles incidence, and international recommendations indicate that there is no need for predictive allergological work-up and that the MMR vaccine is well tolerated in egg-allergic patients. We report on the case of a 12-year-old child with severe immediate-type egg allergy. Immediate-reading intradermal skin tests performed prior to the MMR vaccine were positive. Subsequent allergological work-up revealed a gelatin sensitization, and the child tolerated injections of the vaccine given according to a tolerance induction protocol. Gelatin is used as a stabilizer in numerous vaccines and may be responsible for immediate-type hypersentivity reactions to gelatin-containing vaccines. In case of reaction induced by the MMR vaccine, one needs to explore a potential gelatin sensitization/allergy. The MMR vaccine should be given and is well tolerated in patients with immediate-type egg hypersensitivity, even when gelatin sensitization is combined.

Severe drug-induced anaphylaxis: analysis of 333 cases recorded by the Allergy Vigilance Network from 2002 to 2010.

BACKGROUND: A few series of well-documented cases of severe drug-induced anaphylaxis (SDA) are available. METHODS: Cases collected by the Allergy Vigilance Network from 2002 to 2010 were analyzed for clinical signs, causative drugs, and efficacy of a stepwise approach to diagnosis, using skin tests, laboratory tests, and oral challenges. RESULTS: Three hundred and thirty-three cases concerned 300 adults (90.1%) and 33 children (9.9%): 206 females (61.9%) and 127 males (38.1%). Mean age was 42.7 ± 18 years. Anaphylactic shock (76.6%), severe systemic reactions (10.5%), acute laryngeal edema (9%), severe bronchospasm (2.1%), and six fatal cases (1.8%) were recorded. There were 270 cases (81.1%) of ambulatory anaphylaxis. Sixty-three cases (18.9%) occurred during anesthesia. Hospitalization was required in 94.8% of cases. 23.7% of patients were admitted to an intensive care unit. Epinephrine was used in 57.9% of cases. Eighty-four drugs were incriminated: antibiotics (49.6%), muscle relaxants, latex and anesthetics (15%), nonsteroidal anti-inflammatory drugs (10.2%), acetaminophen (3.9%), iodinated or magnetic resonance imaging contrast media (4.2%), immunotherapy and vaccines (3.9%), and other drugs (13%). Among antibiotics, amoxicillin (97 cases), other penicillins (four cases), cephalosporins (41 cases), quinolones (15 cases), and pristinamycin (seven cases) were the most common. The diagnosis of drug hypersensitivity was obtained by skin tests in 72.9%, laboratory tests only in 2.4% of cases, and oral challenges (OCs) only in 3.9% of cases. CONCLUSIONS: Three hundred and thirty-three case reports provided data on drugs involved in severe anaphylaxis. The efficacy of skin tests and poor use of laboratory tests are underlined. Further progress may depend on OCs.

[Allergic and non-allergic hypersensitivity to non-opioid analgesics, antipyretics and nonsteroidal anti-inflammatory drugs in children: epidemiology, clinical aspects, pathophysiology, diagnosis and prevention]. / Les réactions d'hypersensibilité allergique et non allergique aux antalgiques non opiacés, antipyrétiques et anti-inflammatoires non stéroïdiens chez l'enfant : épidémiologie, aspects cliniques, physiopathologie, diagnostic et prévention.

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.

Allergy to betalactam antibiotics in children: results of a 20-year study based on clinical history, skin and challenge tests.

Studies based on skin and challenge tests have shown that 12-60% of children with suspected betalactam hypersensitivity were allergic to betalactams. Responses in skin and challenge tests were studied in 1865 children with suspected betalactam allergy (i) to confirm or rule out the suspected diagnosis; (ii) to evaluate diagnostic value of immediate and non-immediate responses in skin and challenge tests; (iii) to determine frequency of betalactam allergy in those children, and (iv) to determine potential risk factors for betalactam allergy. The work-up was completed in 1431 children, of whom 227 (15.9%) were diagnosed allergic to betalactams. Betalactam hypersensitivity was diagnosed in 50 of the 162 (30.9%) children reporting immediate reactions and in 177 of the 1087 (16.7%) children reporting non-immediate reactions (p<0.001). The likelihood of betalactam hypersensitivity was also significantly higher in children reporting anaphylaxis, serum sickness-like reactions, and (potentially) severe skin reactions such as acute generalized exanthematic pustulosis, Stevens-Johnson syndrome, and drug reaction with systemic symptoms than in other children (p<0.001). Skin tests diagnosed 86% of immediate and 31.6% of non-immediate sensitizations. Cross-reactivity and/or cosensitization among betalactams was diagnosed in 76% and 14.7% of the children with immediate and non-immediate hypersensitivity, respectively. The number of children diagnosed allergic to betalactams decreased with time between the reaction and the work-up, probably because the majority of children with severe and worrying reactions were referred for allergological work-up more promptly than the other children. Sex, age, and atopy were not risk factors for betalactam hypersensitivity. In conclusion, we confirm in numerous children that (i) only a few children with suspected betalactam hypersensitivity are allergic to betalactams; (ii) the likelihood of betalactam allergy increases with earliness and/or severity of the reactions; (iii) although non-immediate-reading skin tests (intradermal and patch tests) may diagnose non-immediate sensitizations in children with non-immediate reactions to betalactams (maculopapular rashes and potentially severe skin reactions especially), the diagnostic value of non-immediate-reading skin tests is far lower than the diagnostic value of immediate-reading skin tests, most non-immediate sensitizations to betalactams being diagnosed by means of challenge tests; (iv) cross-reactivity and/or cosensitizations among betalactams are much more frequent in children reporting immediate and/or anaphylactic reactions than in the other children; (v) age, sex and personal atopy are not significant risk factors for betalactam hypersensitivity; and (vi) the number of children with diagnosed allergy to betalactams (of the immediate-type hypersensitivity especially) decreases with time between the reaction and allergological work-up. Finally, based on our experience, we also propose a practical diagnostic approach in children with suspected betalactam hypersensitivity.

[Diagnosis of allergic and non-allergic hypersensitivity reactions to commonly used drugs and biological substances in children: diagnostic algorithm]. / Diagnostic des réactions d'hypersensibilité allergique et non allergique aux médicaments courants de l'enfant : arbre décisionnel.

Suspected allergic reactions to drugs and biological substances (anti-infectious drugs and antipyretics, non opioid analgesics and nonsteroidal anti-inflammatory drugs especially) are reported in 5 to 12% of children. Most frequent reactions are morbilliform/maculopapular rashes, urticaria and angioedema. Other cutaneous and respiratory reactions, and severe allergic and non-allergic anaphylactic reactions are rare. The results of studies based on allergological tests and/or microbiological/serological tests strongly suggest that, except for a few types of reactions (anaphylactic and/or immediate reactions, potentially harmful toxidermias) and for very specific drugs (i.e. latex and myorelaxants), most reactions to commonly used drugs and biological substances in children do not result from drug hypersensitivity, but are rather a consequence of the infectious and/or inflammatory diseases for which the drugs have been prescribed. Non-immediate reactions may also result from complex interactions between drugs, immune system and "danger signals" provided or induced by infectious and/or inflammatory diseases. Diagnosis is based above all on a detailed analysis of clinical history, skin tests (if validated), and challenge tests (if indicated). At present, the diagnostic and predictive values of in vitro tests exploring immediate (specific IgE determination, histamine and leukotriene release tests, basophil activation test) and non-immediate type (lymphocyte activation tests, and cytokine assays in the supernatant of activated blood mononuclear cells) of drug hypersensitivity are not validated.

Anaphylaxis to the 23-valent pneumococcal vaccine: a second explored case by means of immediate-reading skin tests with pneumococcal vaccines.

Anaphylaxis to pneumococcal vaccines is rare. In the only one child with anaphylaxis to a first injection of the 23-valent pneumococcal vaccine that has been explored, skin tests and specific IgE determination diagnosed immediate-type hypersensitivity to pneumococcal antigens. We report the case of a child who tolerated three injections of the 7-valent pneumococcal vaccine, but experienced anaphylaxis to a fourth injection of the 23-valent vaccine. Immediate responses in skin tests diagnosed immediate-type hypersensitivity to the two vaccines. Immunizations with the 7-valent pneumococcal vaccine may induce IgE-dependent sensitization to pneumococcal antigens, responsible for anaphylaxis to subsequent injections of pneumococcal vaccines.

[Allergic and non-allergic hypersensitivity reactions to toxoid-containing vaccines]. / Les réactions d'hypersensibilité allergique et non allergique aux vaccins contenant des anatoxines.

Most allergic (like) reactions to vaccines are reported in patients immunized with diphtheria and tetanus toxoid-containing vaccines. Local inflammatory reactions are the most frequent, but most of them are non-specific. Diagnosis of Arthus-type reactions is based on clinical history and specific IgM/IgG anti-toxoid determination. For other local reactions (persistent nodules, sterile abscesses, etc.), diagnostic value of non-immediate responses in skin tests varies with clinical symptoms and substances involved. Immediate responses in skin tests and specific antibody determination have good diagnostic and/or predictive value in anaphylaxis and immediate and accelerated urticaria and angioedema. Although a few generalized non-immediate reactions may result from toxoid-specific semi-late or delayed-type hypersensitivity, most reactions are non-specific. Withholding booster injections is advised if specific IgM/IgG levels are high. If the levels are low, sequential intramuscular injections of mono- or paucivalent vaccines are usually tolerated. However, injections of the vaccine should be performed using a "desensitization" procedure in patients reporting anaphylaxis and immediate or accelerated urticaria or angioedema.

Pharmacovigilance of drug allergy and hypersensitivity using the ENDA-DAHD database and the GALEN platform. The Galenda project.

Nonallergic hypersensitivity and allergic reactions are part of the many different types of adverse drug reactions (ADRs). Databases exist for the collection of ADRs. Spontaneous reporting makes up the core data-generating system of pharmacovigilance, but there is a large under-estimation of allergy/hypersensitivity drug reactions. A specific database is therefore required for drug allergy and hypersensitivity using standard operating procedures (SOPs), as the diagnosis of drug allergy/hypersensitivity is difficult and current pharmacovigilance algorithms are insufficient. Although difficult, the diagnosis of drug allergy/hypersensitivity has been standardized by the European Network for Drug Allergy (ENDA) under the aegis of the European Academy of Allergology and Clinical Immunology and SOPs have been published. Based on ENDA and Global Allergy and Asthma European Network (GA(2)LEN, EU Framework Programme 6) SOPs, a Drug Allergy and Hypersensitivity Database (DAHD((R))) has been established under FileMaker((R)) Pro 9. It is already available online in many different languages and can be accessed using a personal login. GA(2)LEN is a European network of 27 partners (16 countries) and 59 collaborating centres (26 countries), which can coordinate and implement the DAHD across Europe. The GA(2)LEN-ENDA-DAHD platform interacting with a pharmacovigilance network appears to be of great interest for the reporting of allergy/hypersensitivity ADRs in conjunction with other pharmacovigilance instruments.

[Allergic and pseudoallergic reactions to analgesics, antipyretics and non-steroidal anti-inflammatory drugs]. / Les réactions allergiques et pseudoallergiques aux antalgiques, antipyrétiques et anti-inflammatoires non stéroïdiens.

Antalgics, antipyretics and non-steroidal anti-inflammatory drugs (NSAIDs) 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 or anaphylactoid reactions, potentially harmful toxidermias) are rare. In a few patients, reactions may result from a specific (allergic) hypersensitivity (HS), 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) HS (intolerance), with a frequent cross-reactivity between the various families of antalgics, antipyretics and NSAIDs, including acetaminophen (paracetamol). Based on a convincing clinical history and/or positive responses in challenge tests, intolerance to antalgics, antipyretics and NSAIDs has been diagnosed in 13 to 50% of the patients with allergic-like reactions to these drugs. Risk factors for HS to antalgics, antipyretics and NSAIDs are a personal atopy and age. In our experience, 50% of the children with allergic-like reactions to antipyretics, antalgics and NSAIDs were diagnosed intolerant to these drugs. Risk was high in children reporting reactions to NSAIDs (aspirin, ibuprofen) and lower in children reporting reactions to paracetamol. All the children intolerant to paracetamol were also intolerant to NSAIDs. In contrast, most children with NSAID intolerance were tolerant to paracetamol. A personal history of atopy and a mean age >or= 8 years were significant risk factors for intolerance to antalgics, antipyretics and NSAIDs.