Drug Allergy

Drug hypersensitivity reactions to chemotherapy agents are an important problem that Allergy Departments should be proactively prepared to confront, by meeting the necessary high standards to offer optimal management pathways, including high-risk techniques such as drug provocation testing or rapid drug desensitisation, which will cost-effectively improve the prognosis of many patients. Comprehensive risk management strategies, access to expert staff, specific diagnostic techniques, and a dedicated allergy-led area are fundamental to ensure safety. In this manuscript, we will explore current diagnostic and management pathways for hypersensitivity reactions to chemotherapy agents.

Palabras clave: Alergia a medicamentos. Desetiquetado. Provocación controlada. Desensibilización. Pruebas cutáneas. De-labelling is becoming paramount in drug allergy pathways[1]. However, data on de-labelling patients with reactions to chemotherapy and biologics is lacking, and it is limited to a few specialised centres with specific populations[2-4]. A

Lesi Vesikobulosa merupakan lesi berisi cairan jernih dan berada pada lapisan epitel, ruptur serta menimbulkan ulserasi. Lesi vesikobulosa dalam rongga mulut memiliki gambaran klinis, sehingga dibutuhkan pemeriksaan penunjang dalam menentukan diferensial diagnosis untuk tatalaksana perawatan yang tepat.

The case of a 34-year-old woman with melasma is presented. She had been treated by a dermatologist who used a Cosmelan® 1 mask, after which she suffered a facial oedema and erythema that involved the eyelids and lasted for 2 days. She continued the treatment with home applications of Cosmelan® 2 with initially satisfactory cosmetic effect; however, during the treatment she continuously had mild erythema and pruritus. Discontinuation of the treatment resulted in a resolution of the dermatitis and a rapid recurrence of melasma on her face. Photopatch testing was carried out with common photohaptens, as well as with the patient's own cosmetics. Tests with Cosmelan® 2 led to the clear allergic reaction with a rapidly developing postinflammatory hiperpigmentation in the test area. This reaction was somewhat paradoxical for a cosmetic that is marketed as a remedy against hyperpigmentation (melasma). The final diagnosis was allergic contact dermatitis to Cosmelan® 2 with post-inflammatory hyperpigmentation. Similar, yet less pronounced hyperpigmented allergic reactions also developed to the patient's shampoo and bath gel. The present report seems to be the first medical account of allergy to Cosmelan®; however, an Internet search revealed messages posted by 7 people describing similar adverse effects encountered after Cosmelan® treatment, some of which were commented on by dematologists that these might indeed have been allergic reactions. Doctors and patients using Cosmelan® should be aware of the possibility of such side-effects.

"Too many patients with photoallergy remain undiagnosed due to unsatisfactory knowledge among doctors and limited access to photopatch testing. The objectives of this study were to analyze the frequency of patients requiring diagnostic work-up for photoallergic contact dermatitis among dermatology patients, and to identify the causative photosensitizers. This prospective study involved 1000 consecutive, first-referred dermatology outpatients. All patients with a history of dermatitis induced or aggravated by exposure to light were qualified for photopatch testing. In the study group, 36 (3.6%; 95%CI: 2.4-4.8%) persons required photopatch testing based on their clinical symptoms. As the total number of patients requiring patch tests of
any kind amounted to 205, the percentage of photopatch tested patients among all patch-tested patients was 17.5% (95%CI: 12.2-22.8%). Photoallergic contact dermatitis was ultimately confirmed in 15 (1.5%; 0.7-2.3%) persons: 7 females and 8 males aged 6-60 (median 33) years. Nine patients turned out photoallergic to at least one nonsteroidal antiinflammatory drug, with ketoprofen photoallergy being most frequent (5 patients, in each case clinically relevant), followed by etofenamate (4 non-relevant reactions) and diclofenac (1 relevant reaction). Five patients were positive to at least one organic sunscreen, most frequently to benzophenone-3 (2 patients). “Classical” contact allergy to tested photohaptens was found in 15 persons, including 7 with coexisting photoallergy. In conclusion, patients requiring diagnostic work-up for photoallergy constitute a relevant group among dermatology patients, therefore, it seems advisable that all second-level dermatology referral centers be capable of photopatch testing. Due attention should also be paid to photoallergy in dermatology training."

Background: Beta-lactam allergy is overdiagnosed. Diagnosis of penicillin allergy has been associated with a greater use of hospital resources and an increased risk of antibiotic-resistant infections, although this issue remains poorly studied in children. We aimed to compare patient characteristics and use of hospital resources in hospitalized children with and without a record of penicillin allergy. Methods: We identified all hospitalizations in children labelled as being allergic to penicillin in a database containing all hospitalizations in Portuguese public hospitals between 2000 and 2014, and compared these with a similar number of age-, sex-, and main diagnosis-matched hospitalizations without a penicillin allergy label. Comparisons were made for length of hospital stay, comorbidities (Charlson Comorbidity Index), in-hospital mortality, and hospitalization costs. Results: We identified 1,718 hospitalizations corresponding to children labelled as penicillin-allergic. Compared with patients without such a label, these children had longer hospital stays (mean 5 vs. 4 days, p = 0.03) and a higher comorbidity index (mean 0.11 vs. 0.09, p < 0.001). Hospitalization costs were also higher (EUR 2,071 vs. 1,798), but the difference was not significant (p = 0.12). Conclusions: Hospitalizations of children labelled as allergic to penicillin are associated with longer hospital stays, more comorbidities, and a tendency towards higher hospitalization costs. An accurate diagnosis of penicillin allergy based on clinical history and confirmatory tests is therefore essential in all paediatric patients.

Las reacciones alérgicas y seudoalérgicas en el curso de la anestesia provocan
problemas potencialmente graves que deben conocerse y en lo posible
evitarse. En el presente estudio hacemos una revisión para analizar los criterios
diagnósticos, preventivos y terapéuticos de las reacciones alérgicas y
seudoalérgicas que se producen durante la anestesia general. Se realizó una
búsqueda bibliográfica en Pubmed desde 1963 hasta marzo de 2005. Se seleccionaron
los trabajos originales y las revisiones sobre las reacciones alérgicas
en la anestesia general utilizando los siguientes descriptores para la
búsqueda: “anaphylaxis AND anesthetics”. La bibliografía relevante incluye
401 citas, de las cuales 333 (72 de las cuales son revisiones) cumplen los
criterios de selección. Los fármacos que aparecen más frecuentemente implicados
en la anestesia son los relajantes musculares. La sensibilización a
látex figura en segundo lugar, y con menor frecuencia otros medicamentos
como los antibióticos, los expansores del plasma y los opiáceos. Una buena
anamnesis previa a la anestesia (consulta preanestésica) y la realización del
estudio en vivo/de laboratorio (según se considere) son las herramientas para
disminuir o evitar estas reacciones. La colaboración entre especialidades
médicas se revela una vez más como fundamental para una buena práctica
clínica

The broad applicability of allergen-specific immunotherapy for the
treatment  and  eventual  prevention  of  Ig  E -  mediated  allergy  is
limited by the poor quality and allergenic activity of natural allergen
extracts that are used for the production of current allergy vaccines.
Recombinant allergens equalling their natural counterparts have been
produced for diagnosis and immunotherapy, and a large panel of
genetically  modified  allergens  with  reduced  allergenic  activity  has
been characterized to improve safety of immunotherapy and explore
allergen-specific prevention strategies. Recombinant allergens can be
produced as defined molecules with consistent quality and unlimited
amounts  according  to  the  corresponding  DNA  template.  The
recombinant  allergen-based  vaccination  strategies  will  be  generally
applicable to most allergen sources, including respiratory, food and
venom allergens and allow producing safe allergy vaccines for the
treatment of the most common forms of IgE-mediated allergies.

Stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) belongs to the
mitogen-activated protein kinase (MAPK) family and plays an important role in many
biological contexts. JNK is deeply involved in several serious human disorders,
including inflammation, obesity, diabetes, neuronal disease and cancer. Accordingly,
JNK has been recognized as an appropriate target for the treatment of these diseases,
and much effort has been expended over the past 15 years to isolate JNK inhibitors that
can inactivate this kinase. In 2001, the compound SP600125 was reported as the first
JNK-specific inhibitor. Many researchers have subsequently employed SP600125 in in
vitro and in vivo models to evaluate whether certain disease-associated events are
JNK-dependent. Indeed, more than 1300 studies citing the use of SP600125 as a JNK
inhibitor in cell cultures and animal models have been reported. However, although
SP600125 has been employed successfully to inhibit JNK in several situations, there
have been questions about its specificity for JNK. In this article, we review both the
usefulness of SP60125 as a JNK inhibitor and the limitations to its specificity.

Nickel is a chemical element found ubiquitously in the environment and is used with a high frequency worldwide. Nickel hypersensitivity could give rise both to contact dermatitis and to systemic contact dermatitis, the latter, as expression of ingestion or other systemic exposure to a contact allergen. The common clinical presentation of nickel allergic contact dermatitis (ACD) is more often a vesicular pruritic dermatitis in sites of prolonged skin contact with nickel-containing items. Patients can develop acute (bright red rash, edema and vesicle), subacute (less erythematous and edematous lesions, minimal vesiculation, and excoriation) and chronic manifestations (fissuring, scaling, excoriation and mild form of erythema). Systemic contact dermatitis is induced in sensitized individuals when they are exposed to a hapten systemically. In the detection of contact allergy, and in the diagnosis of ACD, patch test is the generally accepted method of choice and the “gold standard”. Their execution increases the probability of correct diagnosis, shortens the time lapse between first visit and final diagnosis, increases the chance for full remission, and reduces therapy costs. Management of nickel allergy is still complex for dermatologists. Between 1994 and 2009, nickel allergy showed a decreased in morbidity; however, after 2000, there was no significant decrease. Exposure to nickelcontaining products exceeding the permitted limit may explain the high persistence of nickel contact allergy in population. In 2001 the European Union, to reduce the exposure to nickel, introduced standards for the productions of tools intended for prolonged skin contact.

Delayed drug allergy reactions (DDAR) are potentially fatal. Certain human leukocyte antigen (HLA) alleles have been associated with delayed allergy reactions following the administration of particular drugs. Examples are HLA-B * 57: 01 (abacavir), HLA-B * 15: 02/HLA-A * 31: 01 (carbamazepine), and HLA-B * 58: 01 (allopurinol). Based on the identification of these associations, it may now be possible to prevent certain allergy reactions that were, until recently, considered unpredictable. In this review, we will focus on the pharmacogenetics of the best-studied associations between specific HLA alleles and delayed allergy reactions and describe the pathogenesis models proposed so far. Finally, we will evaluate the genetic screening strategies available and discuss the clinical relevance of a better understanding of the immunogenetics and mechanisms involved in DDAR.

BACKGROUND: In early clinical trials, infusion reactions during the administration of taxanes were managed using systematic premedication with antihistamines and corticosteroids prior to standard infusions. Consequently, these premedications are also administered prior to rapid drug desensitization (RDD) with taxanes. However, their role in RDD has not been studied.
OBJECTIVE: To assess the need for premedication with antihistamines and corticosteroids to prevent hypersensitivity reactions in RDD to paclitaxel.
METHODS: Over a 4-year period, we selected patients with confirmed hypersensitivity to paclitaxel (positive skin testing and/or drug provocation testing results) who had received paclitaxel through RDD. These patients were assigned to 2 prospective non-inception cohorts: one cohort premedicated with antihistamine and corticosteroids and another cohort that was not.
RESULTS: We assessed 66 paclitaxel-reactive patients, of whom 22 met the inclusion criteria. There were no significant differences in tolerance to RDD between the cohorts.
CONCLUSIONS: Administering systematic premedication with corticosteroids and antihistamines had no significant effect on the effectiveness or safety of RDD in patients with confirmed hypersensitivity to paclitaxel in the study population. Moreover, these premedications can mask the early signs of hypersensitivity and delay treatment. We believe that systematic premedication with these drugs for patients undergoing RDD should be carefully and individually assessed if their only purpose is to prevent breakthrough reactions during RDD.

Background: Healthcare workers are reported to be in a higher risk for drug allergy, due to their professional exposure. This study intends to measure the prevalence of these allergies in healthcare workers in Albania. Method: A cross-sectional study was conducted at the University Hospital Centre "Mother Theresa" where 662 nurses were requested to fill up a questionnaire. 639 of them accepted to answer the questionnaire. The questionnaire has detailed questions about the drug that caused the allergy, its nature, treatment, and diagnostics tests. The RR and the chi-square were calculated between three subgroups; 0-9, 10-19 and >20 years of work in health services, with 95% CI. The data were analyzed with MS Excel 2007 and PASW Statistics 18.

Delayed drug allergy reactions (DDAR) are potentially fatal.
Certain human leukocyte antigen (HLA) alleles have been associated
with delayed allergy reactions following the administration
of particular drugs. Examples are HLA-B * 57: 01
(abacavir), HLA-B * 15: 02/HLA-A * 31: 01 (carbamazepine), and
HLA-B * 58: 01 (allopurinol). Based on the identification of
these associations, it may now be possible to prevent certain
allergy reactions that were, until recently, considered unpredictable.
In this review, we will focus on the pharmacogenetics
of the best-studied associations between specific HLA alleles
and delayed allergy reactions and describe the pathogenesis
models proposed so far. Finally, we will evaluate the
genetic screening strategies available and discuss the clinical
relevance of a better understanding of the immunogenetics
and mechanisms involved in DDAR.

The purpose of this study was to compare the management of patients with a history of penicillin allergy between allergists and non-allergists in Thailand. A questionnaire was distributed to Thai physicians by online survey. The answers from 205 physicians were analyzed. The discrepancy of penicillin allergy management between allergists and non-allergists was clearly demonstrated in patients with a history of an immediate reaction in the presence of penicillin skin test (P < 0.01) and in patients with a history of Stevens-Johnson syndrome (P < 0.05) from penicillin. Allergists are more willing to confirm penicillin allergic status, more likely to carefully administer penicillin even after negative skin test, but less concerned for the potential cross-reactivity with 3rd and 4th generation cephalosporins, compared to non-allergists. The lack of penicillin skin test reagents, the reliability of penicillin allergy history, and medicolegal problem were the main reasons for prescribing alternate antibiotics without confirmation of penicillin allergic status. In summary, the different management of penicillin allergy between allergists and non-allergists was significantly demonstrated in patients with a history of severe non-immediate reaction and in patients with a history of an immediate reaction when a penicillin skin test is available.

Background: Hypersensitivity reactions to oxaliplatin may affect prognosis by jeopardizing the timely completion of scheduled treatment sessions or by forcing reactive patients into unexpected changes in therapy. Rapid drug desensitization (RDD) enables these patients to receive their first-choice treatments safely. However, the possible effects of RDD on the efficacy of oxaliplatin have never been studied.
Objective: The objective of this study was to evaluate the effect of RDD on survival rates in oxaliplatin-hypersensitive patients.
Methods: We performed a 7-year retrospective study to compare survival between oxaliplatin-hypersensitive cases (patients receiving oxaliplatin by RDD) and nonallergic controls (patients receiving standard oxaliplatin infusions). The primary endpoint of this study was overall survival (OS) in cases and controls (Kaplan-Meier method with log-rank test comparisons).
Results: OS was 23.7 months (95%CI, 15.3-30.9) for the 67 cases who underwent 337 RDDs, while for controls (n=143), OS was 34.5 months (95%CI, 21.7-55.5). There were no significant differences between the groups (HR, 1.42; 95%CI, 0.93-2.17; P=.104).
Conclusions: Survival outcomes of oxaliplatin-hypersensitive patients who received oxaliplatin via RDD did not differ significantly from those of control patients who received oxaliplatin via standard administration. Receiving oxaliplatin by means of RDD might be an effective therapeutic alternative for oxaliplatin-hypersensitive patients.

Intranasal glucocorticoids are the treatment of choice in the therapy of rhinitis. The differences in efficiency of particular medications
proven by therapeutic index may result from differences in composition of particular formulations as well as from diverse deposition in nasal cavities.
All intranasal medications deposited mainly on the anterior part of inferior turbinate. Deposited also on the anterior part of the middle nasal turbinate,
marginally embracing a fragment of the central part of this turbinate as well together with deposition in the middle and superior nasal meatus
reaching the region of nasal ceiling and olfactory field. Mometasone furoate preparation deposited on the anterior part of the inferior turbinate and
central part of this turbinate alike. The area of mucous membrane of lateral wall of nasal cavity on which mometasone furoate deposited was similar
to the area achieved after the application of fluticasone propionate preparation but much greater than in the case of fluticasone furoate. The interaction
of the air flow with the layer of deposited fluid plays a major role in the deposition of the drug in the nasal cavity, therefore it is so important that
the drug does not drain by gravity but remains at the site of deposition which may be reinforced by thixotropic properties of the preparation.

more frequent, in 48%, moderate Persistent AR; followed by mild persistent AR in a 30%, moderate intermittent AR 14%, mild intermittent AR 5% and severe AR only 3%. By applying the questionnaire AdolRQLQ we found moderate affectation of the quality of life in 73% of patients, a severe affectation in only 14% and slight in 13%. However, when performing the correlation between the severity of the disease and the degree of impairment of quality of life, we don't find a proportional relationship as there are patients who see the quality of life decreased significantly, even though the disease is classified as mild and vice versa. For example: 79% mild persistent AR patients scored for moderate affectation of the quality of life, only 13% for slight and 8% severe; while none of the adolescents scored for AR severe deterioration of the quality of life, all of them were classified with mild impairment. Conclusions: Adolescent patients with allergic rhinitis are affected quality of life this involvement is not directly proportional to the severity of the disease. Treatment, in addition to seeking control of symptoms, should provide the support needed to improve their quality of life.

1 ONDERZOEK Lokale verdovingen worden dagelijks toegediend door tandartsen en artsen in vele vakgebieden. Wereldwijd worden elke dag meer dan 5 miljoen injecties met een lokaal anestheticum gegeven. 1 Desondanks komen bijwerkingen maar zelden voor. Meestal gaat het daarbij om vasovagale reacties, en slechts zelden om een IgE-gemedieerde allergische reactie. 2 Bij een reactie op een lokaal anestheticum zijn artsen en patiënten beducht voor een IgE-gemedieerde allergie vanwege de potentiële ernst van deze reacties. Het doel van allergietesten bij deze patiënten is het aantonen of uitsluiten van een IgE-gemedieerde reactie en het vinden van een veilig alternatief. Veel patiënten worden naar de allergoloog of dermatoloog verwezen met de vraag of zij allergisch zijn voor lokale anesthetica, maar de incidentie van een bewezen allergie daarvoor is erg laag volgens de huidige literatuur. Van patiënten die met deze vraag waren verwezen onderzochten wij retrospectief in 2 klinieken hoe vaak een allergie voor lokale anesthetica bewezen kon worden. Tevens geven wij in dit artikel een overzicht van de huidige stand van zaken van de diagnostiek, en aanwijzingen voor de dagelijkse praktijk.

Text: Background: Generally atopy is defined as a genetic disposition to develop allergic diseases such as allergic rhinitis, asthma, or atopic dermatitis. It is also known as an increased capacity to produce IgE response to common environmental antigens. This study intends to measure the relative risk of atopic individuals to develop allergy to food, drug and latex. Method: In a cross-sectional study, 639 nurses (from 662 that were asked for) at the UHC "Mother Theresa" in Tirana, accepted to fill up a questionnaire where questions about personal atopy, food, drug and latex allergy were included. 589 were females and they have a mean age 43.28 (+10.71) years. We considered atopic every person that has at least any of the atopic diseases (allergic rhinitis, asthma, or atopic dermatitis). The chisquare test and the RR with a 95% CI were calculated for each case. MS Excel 2007 and PASW Statistics 18 were used to analyze the data. Results: 20.81% (133) of nurses reported to have had at least one of the atopic diseases. No differences in prevalence of atopy were observed between two sexes. The RR for the atopic individuals to develop allergies to foods resulted 4.44 (95% CI=2.42 to 8.16, p< 0.05) while the RR for this category to develop allergic symptoms to latex were 5.08 (95% CI=3.17 to 8.13, p< 0.05). Atopic individuals had a RR of 1.45 to develop allergic symptoms to different drugs (95% CI=0.94 to 2.23, p< 0.05) compared to non-atopic ones. Conclusion:

Text: Background: Allergies are increasing among Albanian children. For now, studies about their prevalence are exclusively focused in Tirana, the capital of Albania. This study intends to check the prevalence in Gjirokastër, one of the southern districts of Albania. Method: This is a cross-sectional survey where participated all the children of the third and fourth level of the elementary schools of the Gjirokastër town in 2010. 313 children with a mean age of 9.34±1.16 years old, 139 (44.4%) males, received a questionnaire that was filled up by their parents. The questionnaire included ISAAC questions on ever wheezing, current wheezing, allergic diseases and allergic reactions. The data were analysed with PASW Statistics 18. Results: 23.72% (74) had experienced at least once wheezing during their life, but only 5.81% (18) had experienced wheezing last year. 2.59% (8) answered positively to the asthma ever question, and 23.72% to the allergic rhinitis ever. 18.53% respond positively to the question "Have you ever had any severe and sudden allergic reaction?", 6.71% (21) blamed antibiotics (mostly beta-lactamides), 5.11% insect stings and 4.15% (13) different foods. Conclusion: These were the first data on the epidemiology of asthma and allergy out the capital of Albania. Furthermore it can be seemed clearly a higher prevalence of wheezing, asthma and allergic rhinitis compared to the ISAAC findings on Tirana. Other studies could be able to identify the factors that impact these differences.

Dapsone 100 mg/pyrimethamine 12.5 mg (Maloprim; Beacons Chemicals Pte Ltd, Singapore) is routinely prescribed for antimalarial chemoprophylaxis in military servicemen in Singapore who are not glucose-6-phosphate dehydrogenase-deficient.We report a series of three male National Servicemen with hypersensitivity syndrome from Maloprim.The three patients were diagnosed with hypersensitivity syndrome based on the presence of features of a drug hypersensitivity syndrome including fever, lymphadenopathy, maculopapular exanthema, hepatitis, and definite exposure to weekly Maloprim alone. A mild Coombs positive hemolytic anemia was also observed in one patient. All the clinical, hematologic, and biochemical derangements normalized within 3 months of tapering regimens of moderate-dose prednisolone.Drug hypersensitivity syndromes can occur even on low-dose, weekly drug regimens. Hypersensitivity syndrome from weekly Maloprim is potentially reversible when recognized and treated early.

Non-steroidal Anti-Inflammatory Drugs (NSAIDs) are among the most prevalent drugs inducing hypersensitivity reactions. The aim of this analysis was to estimate the prevalence of NSAIDs-induced respiratory symptoms in population across Europe and to assess its association with upper and lower respiratory tract disorders. The GA(2) LEN survey was conducted in 22 centers in 15 European countries. Each of 19 centers selected random samples of 5000 adults aged 15-74 from their general population, and in three centers (Athens, Munich, Oslo) a younger population was sampled. Questionnaires including questions about age, gender, presence of symptoms of asthma, allergic rhinitis, chronic rhinosinusitis, smoking status and history of NSAIDs-induced hypersensitivity reactions were sent to participants by mail. Total 62, 737 participants completed the questionnaires. The mean prevalence of NSAIDs-induced dyspnea was 1.9% and was highest in the three Polish centers [Katowice (4.9%), Krakow (4.8%...

Although extensively studied in adults, nonsteroidal anti-inflammatory drug (NSAID) hypersensitivity in children, especially in young children, remains poorly defined. Pediatricians, prescribing antipyretics for children, rarely encounter significant problems, but the few epidemiologic studies performed show conflicting results. Although it is clear that some patients with acetylsalicylic acid (ASA)sensitive asthma have their clinical onset of disease in childhood and bronchoconstriction after ASA challenge is seen in 0 to 22% of asthmatic children so challenged, ibuprofen at antipyretic doses may cause acute respiratory problems only in a very small number of mild to moderate asthmatics. The recently elucidated mechanism of action of acetaminophen may explain some occurrences of adverse reactions in patients with cross-reactive NSAID hypersensitivity on the basis of its inhibitory activity on the newly described enzyme, cyclooxygenase (COX)-3. This nonspecific sensitivity to inhibition of COX is most likely genetically determined and shows a remarkable association with atopic disease even in the very young age group and possibly an increased predilection in specific ethnic groups. This review summarizes state-of-the-art published data on NSAID hypersensitivity in preschool children.

Purpose To compare acute ocular complications of toxic epidermal necrolysis (TEN) following treatment with high-dose human intravenous immunoglobulin (IVIG) with a historical cohort not treated with IVIG. Methods Retrospective, historically controlled study. In all, 10 consecutive patients with TEN (treatment cohort) presenting between 1 July 2001 and 30 June 2002. Totally, 18 consecutive patients with TEN (historical cohort). Setting Tan Tock Seng Hospital, Singapore. The treatment cohort received high-dose IVIG (2 g/kg body weight over 2 days). Patients' records were retrospectively reviewed for their demographic characteristics, causative drug, treatment, ocular involvement (if any, as assessed by an ophthamologist), and its severity. The historical cohort comprised patients coded with a diagnosis of TEN (ICD Code 695.1) between 1 July 1995 and 30 June 2001. Results Nine (90%) of 10 patients treated with IVIG had ocular involvement. Phenytoin was the implicated drug in three (37.5%) patients. Of the nine patients, 1 died of septic shock. Of the eight survivors, IVIG was initiated immediately upon onset of TEN as all the patients were hospitalized by the time of onset of an exanthema. Acute ocular complications were mild in two (25%) (lid oedema or mild conjunctival injection), moderate in four (50%) (pseudomembranes) and severe in two (25%) (nonhealing epithelial defect with visual loss and symblepharon). In total, 10 (55.6%) of 18 patients in the historical cohort with TEN had acute ocular involvement. Two patients died. Ocular involvement in survivors was mild in five (62.5%) cases and moderate in three (37.5%), with no severe cases. Conclusions IVIG did not appear to reduce the severity of visually significant ocular complications. Larger studies are needed to confirm this finding.

This study shows that drug provocation testing (aka drug challenge) with chemotherapy and biological agents can be implemented with good safety results. This leads to delabeling a significant percentage of patients and reducing the number of unnecessary drug desensitization. On another note, it discusses the importance of allergy-led multidisciplinary teams as the key to success in the use of allergy-specific techniques such as skin testing, drug challenge or RDD, to correctly assess and manage these patients. Additionally, this article shows the efficacy and safety of using the Brigham & Women's Hospital Rapid Drug Desensitization protocol on a different population with a different profile of patients.

BACKGROUND: Large-scale studies of drug provocation testing (DPT) or rapid drug desensitization (RDD) for hypersensitivity to antineoplastics and biologicals are scarce and limited to a few institutions.
OBJECTIVE: Our aim was to review our experience with DPT and RDD in a large number of patients with a history of hypersensitivity to antineoplastics and biologicals and summarize the practical implications of that experience.
METHODS: This was a 7-year prospective, observational, longitudinal study with reactive patients referred to the Desensitization Program at Ramon y Cajal University Hospital (RCUH). Patients were selected after following our systematic and validated diagnostic approach (clinical history, skin test, risk assessment, specific IgE, DPT) before RDD. Candidate patients underwent RDD using the RCUH protocol. Cetuximab reactors underwent 1-bag RDDs.
RESULTS: A total of 1027 intravenous RDDs were performed using the RCUH protocol (399 platins, 395 taxanes, 178 biologicals, 55 other drugs), and 1026 were successfully accomplished in the 186 patients (of 515 referred patients) who met inclusion criteria for RDD. No breakthrough reactions occurred in 88% of RDDs. Most breakthrough reactions were mild. A total of 341 DPTs were performed, and 229 results were negative (67%). DPTs helped exclude hypersensitivity in 44%
(229 of 515) of referred patients. In addition, 77 one-bag RDDs were performed in 6 cetuximab-reactive patients.
CONCLUSIONS: This experience allows us to describe general management plans, as well as specific patient phenotypic patterns, predictors for reactions, and risk considerations that need a tailored approach (taking into account the 3 prominent drug categories: platins, taxanes, and biologicals).

We describe an important number of confirmed hypersensitivity reactions to leucovorin during a one-year period. Leucovorin can be included in FOLFOX/FOLFIRI regimes and be a hidden allergen (making doctors falsely think the reaction was caused by oxaliplatin or irinotecan). We show how patients reacting to leucovorin may also react to l-isomer calcium folinate and we explore the issue of cross-reactivity with oral folinate. We believe protocols studying FOLFOX/FOLFIRI hypersensitivity reactions should be undergone by drug allergy experts and include systematic skin testing and drug provocation testing with folinic acid, to avoid infra-diagnosis and its resulting risks. Moreover, we report the first intravenous rapid desensitization to leucovorin in a reactive patient (confirmed by drug provocation testing).

Aim: Hypersensitivity reactions to carboplatin are not an infrequent adverse event in ovarian cancer patients. However, reintroduction of platinum-containing schedules is the standard of care in platinum-sensitive recurrent ovarian cancer. Rapid desensitization is a procedure for gradual reintroduction of drug. It allows a safe administration of medications that are beneficial for the management of patients after certain types of hypersensitivity reactions. It is indicated in cases in which there are no reasonable therapeutic alternatives. Methods: We performed a descriptive retrospective study of high-grade ovarian cancer patients with known carboplatin hypersensitivity reactions that were treated with a 13-steps rapid desensitization protocol with 3 different solutions and infusion rates. The procedure followed a mathematic model (gradual increases with a relationship between doses following a geometric series) which is called logarithmic rapid desensitization protocol (LRDP). The aim was to describe the safety of the LRDP in terms of number and severity of infusion reactions and the effectiveness in the rate of cycles completely administered. Results: Four different patients diagnosed with recurrent platinum-sensitive ovarian cancer with a previous infusion reaction were included. LRDP was administered in 19 different cycles. LRDP was administered safety in all 19 cycles, only 2 patients had a mild cutaneous reaction in 4 different cycles during LRDP (21.05%). The foreseen dose of carboplatin was fully administered in all cycles.

Background: Penicillin allergy is commonly reported, but only a minority of claimants has a confirmed diagnosis. Nevertheless, patients labeled as having penicillin allergy are treated with second-line antibiotics, which are more expensive and less effective, possibly increasing the risk of drug-resistant infections. Objective: To compare hospitalizations with and without registration of penicillin allergy concerning their morbidity and hospital resource use. Methods: We analyzed a national administrative database containing a registration of all Portuguese hospitalizations from 2000 to 2014. All episodes occurring in adults with a penicillin allergy registration were compared with an equal number of hospitalizations without such registration and matched for inpatients' age, sex, and main diagnosis. We compared those episodes concerning their length of stay, hospital price charges, comorbidities, and frequency of drug-resistant infections. Differences between medical and surgical hospitalizations were explored. Results: Hospitalizations with registration of penicillin allergy (n = 102,872) had a longer average length of stay than the remainder episodes (8 vs 7 days; P < .001) and higher hospital charges (3,809.0 vs 3,490.0 USD; P < .001). Inpatients with penicillin allergy registration also had a higher mean Charlson Comorbidity Index (0.91 vs 0.76; P < .001) and a significantly higher frequency of infections by several agents, including methicillinresistant Staphylococcus aureus, Enterococcus species, and Escherichia coli. Among surgical episodes, septicemia was 1.2-fold more frequent among penicillin allergy cases. Conclusion: Hospitalizations with registration of penicillin allergy are associated with increased economic costs and frequency of infections by drug-resistant agents, reinforcing the need to establish a correct diagnosis of penicillin allergy. the respective abstract was published (Sousa-Pinto B, Fernandes A, Araújo L, et al. Clinical and economic burden of hospitalizations with registry of penicillin allergy. J Allergy Clin Immunol. 2017;139[suppl]:AB59).