Negative Skin Test Research Articles

Results of penicillin skin testing in patients with suspected penicillin allergy - the Qatar experience.

Background: Unverified penicillin allergy has been linked to adverse patient events and increased healthcare expenditure owing to the usage of broad-spectrum, expensive antibiotics. Penicillin allergy test is the gold standard to diagnose penicillin allergy; and in this study, we present data from Qatar which have not been published before.Methods: Patients with a history of penicillin allergy who underwent penicillin allergy testing between January 2015 and December 2020 at the Allergy Division of the Hamad General Hospital were retrospectively reviewed from the division registry. Benzylpenicilloyl-polylysine (PPL) and minor determinant mixture (MDM) kit DAP-penicillin (0.04 mg +0.5 mg)/vial) (penicillin G, amoxicillin (20 mg/vial), and lately clavulanic acid (20 mg/vial) (DAP, Diater, Madrid, Spain) were used for skin and intradermal testing according to published guidelines. Patients with negative skin tests were administered direct oral challenge with amoxicillin/clavulanate (500/125 mg) and observed for 2 hours.Results: Of the 189 charts reviewed, 183 patients had a complete data set for analysis. Patients were predominantly women (n = 132, 72%) with an average age of 42 years. Of these patients, 149 (81.4%) had a history of an immediate allergic reaction to penicillin, 10 had a history of delayed reactions, and 24 had other or undefined reactions. A total of 39 (21.3%) patients were diagnosed with penicillin allergy (30 patients with positive skin test results and 9 using a direct oral challenge).Of the 30 patients with positive skin testing, 5 reacted to PPL, 8 to MDM, 13 to amoxicillin, and 4 to clavulanic acid.Conclusion: Previous studies indicate that 90% patients with a history of penicillin allergy were able to tolerate the drug (10% were truly allergic). Our data showed that 21% were truly allergic to penicillin. This high positive rate can be attributed to the high pretest probability based on the detailed history obtained before the test, which led to the exclusion of patients with symptoms incompatible with penicillin allergy from the test.

Correlation between skin test results and historical manifestations in patients with suspected lidocaine hypersensitivity.

Background: Adverse reactions to local anesthetics (LA) are relatively common; however, true IgE-mediated allergy is extremely rare, estimated to occur in less than 1%. Investigating patients with suspected allergy to LA should begin with a detailed history to exclude other more common operation theater related culprit medications, followed by skin testing. The subcutaneous challenge is considered the gold standard for confirming true IgE-mediated allergy to LA. In this study, we have described the skin prick test results of patients with suspected lidocaine allergy who had historical reaction symptoms typical to IgE-mediated allergic reactions.Methods: The data were retrieved from the allergy procedure log registry for patients who were referred to the allergy clinic with a suspected allergic reaction to lidocaine at the Hamad Medical Corporation between 2016 and 2020. These patients’ symptoms of historical reactions to lidocaine were compared to their skin test results.Result: A total of 7 patients were identified. The skin test result for lidocaine was positive in only 1 patient; his historical reaction was anaphylaxis (urticaria/angioedema and shortness of breath). The remaining 6 patients had a negative result for skin and challenge tests. Of these 6 patients with negative results, 4 had only urticaria/angioedema as historical reactions; 1 had systematic manifestation (tachycardia) along with urticaria/angioedema, and 1 experienced systemic symptoms (shortness of breath, chest pain, and palpitation) with no skin or mucous membrane involvement (Table 1).Conclusion: Negative skin test and subcutaneous challenge with a history of generalized cutaneous symptoms and/or systemic symptoms during the reaction to LA can be attributed to many causes, such as an IgE-mediated reaction against a component other than lidocaine (e.g., latex), medication side effects (adrenaline in combined preparations), and/or symptoms of primary disease (chronic spontaneous urticaria/angioedema).

Contrast Medium Hypersensitivity: A Large Italian Study with Long-Term Follow-Up.

Hypersensitivity reactions (HRs) to contrast media (CM) are a major problem. We compared differences of HRs to iodinated contrast media (ICM) versus gadolinium-based contrast media (GBCM), collecting data on prevalence, type, latency and severity. Secondly, the predisposition to perform new contrast tests, use of premedication and possible appearance of new reactions were explored in a long-term follow-up of 5 years. Clinical data, comorbidities, skin test (ST) results, re-exposure to CM procedures with any new reactions, premedication and CM used were collected. In a retrospective single-center study, 350 patients with mild to moderate HRs were enrolled. Asthma, food allergy, non-allergic drug hypersensitivity and neurologic disease were significantly more frequent in patients with HRs to GBCM compared to the high evidence of cardiovascular disease and history of cancer in patients with HRs to ICM. A marked delay in performing STs was reported by patients with negative results (66 months, p < 0.01). Iomeprol, iopamidol and gadobenic acid were the culprit CM most involved in HRs in patients with positive STs. During follow-up, 7.1% of responders reported new HRs to CM despite negative STs, premedication and infusion of alternative CM in most cases.

Retinitis due to Rickettsia infection

A 67-year-old woman with type 2 diabetes presented to our hospital with decreased left vision for 7 days. On examination, right visual acuity was 20/30, and left visual acuity was 20/50. Intraocular pressures were both normal. Anterior chambers were deep and uninflamed, with bilateral nuclear sclerotic cataracts. There was mild left vitritis, but none in the right eye. Right fundoscopy was normal. Left fundoscopy showed one-disc diameter of unifocal retinitis along the superior vascular arcade (figure A). Left fluorescein angiography revealed late staining in the area of retinitis. The patient was treated presumptively with anti-toxoplasmosis and anti-herpes therapy (oral pyrimethamine [100 mg for the first day then 50 mg daily] and oral sulfadiazine [1 g three times daily] for toxoplasmosis, and intravenous aciclovir [800 mg three times daily] for herpetic retinitis), while awaiting laboratory results. PCR testing of anterior chamber taps were negative for Herpes simplex virus and toxoplasmosis. Negative Treponema pallidum hemagglutination and venereal disease research laboratory test excluded syphilis. Negative QuantiFERON-TB Gold test and tuberculin skin test were negative, and eliminated tuberculosis as a possible cause. Serum angiotensin converting enzyme and lysozyme were normal, which made sarcoidosis an unlikely explanation for the clinical findings. The patient's vision worsened to 20/200 in the left eye. Fundoscopy showed ongoing retinitis with a new retinal haemorrhage and serous macular detachment. She subsequently disclosed having episodes of malaise, headache, myalgia, skin rash (figure B), and fever (maximum 39·5°C; unresponsive to amoxicillin 500 mg three times a day), following travel to rural Algeria. Serology for Rickettsia conorii showed an elevated IgG titer of 1024 g/L, but was negative for IgM. Anterior tap PCR and cutaneous biopsy were negative for Rickettsia. Fundoscopy improved markedly after 7 days of treatment with doxycycline (200 mg daily). After 2 months, visual acuity was 20/20 and the retinitis resolved fully. This case illustrates the importance of careful history taking, and maintaining an index of suspicion for Rickettsia in patients who have travelled to an endemic area and present with fever, skin rash, and retinitis.

Coronavirus disease 2019 vaccine administration in patients with reported reactions to polyethylene glycol- and polysorbate-containing therapeutics

BackgroundPolyethylene glycol (PEG) and polysorbate reactions were initially implicated as a likely risk factor for reacting to coronavirus disease 2019 (COVID-19) vaccines and remain a source of vaccine hesitancy despite increasing evidence that they do not pose an increased risk for COVID-19 vaccine reactions. ObjectiveTo investigate COVID-19 vaccine safety outcomes in patients with reported reactions to PEG- and polysorbate-containing medications and vaccines. MethodsCOVID-19 vaccine safety was reviewed in patients with PEG or polysorbate reactions documented in their electronic medical records at a tertiary academic medical center (cohort 1) and patients referred to Allergy and Immunology with reported PEG or polysorbate reactions (cohort 2). COVID-19 vaccine safety was also reviewed following reported symptoms (onset ≤ 12 hours) to first-dose PEG-containing messenger RNA (mRNA) COVID-19 vaccine (cohort 3). ResultsOf 252 patients in cohort 1 (n = 202) and cohort 2 (n = 50), 236 (94%) received mRNA COVID-19 vaccines (106 Pfizer, 130 Moderna); 235 received both doses. Only 3 patients from cohort 2 developed mild rash following vaccination. None of the 44 patients in cohort 3 with acute symptoms following first-dose mRNA COVID-19 vaccine (27 Pfizer, 17 Moderna) had previously reported PEG or polysorbate reactions. Of these 44 patients, 43 received the second dose and all 3 who developed symptoms following the second dose (1 required epinephrine) had negative PEG skin testing. ConclusionPatients with reported reactions to PEG and polysorbate safely received COVID-19 vaccines. PEG and polysorbate skin testing did not identify patients at risk for first dose or recurrent reactions to COVID-19 vaccines. Screening for PEG and polysorbate allergy may only increase vaccine hesitancy without identifying patients at risk for COVID-19 vaccine reactions.

The Efficacy of Hematoporphyrin Monomethyl Ether Photodynamic Therapy in Adult Patients with Port-Wine Stains: A Retrospective Study.

IntroductionHematoporphyrin monomethyl ether-photodynamic therapy (HMME-PDT) has been showing promising results in the treatment of port-wine stains (PWSs). We evaluated the clinical efficacy and treatment response of HMME-PDT in adult Chinese patients with PWSs.MethodsA single-center retrospective study recruited adult PWS patients with negative HMME skin test results from December 2017 to May 2020. Patients received an intravenous injection of 5 mg/kg HMME and the lesions were exposed to 532 nm LED green light with an irradiation power density of 85–95 mW/cm2 for 20–25 min. Digital photographs were taken before and after two therapy sessions and observed by three blinded dermatologists for clinical response.ResultsA total of 72 patients aged between 18 and 55 years were recruited. There were 65 patients of the flat purple type, 5 of the hypertrophic type, and 2 of the nodular thickening type. Of the 65 patients, 7 showed excellent efficacy (10.77%), 13 patients indicated good efficacy (20.00%), 47 patients showed fair efficacy (64.62%), while 3 cases displayed no improvement (4.62%). All five patients of the purple and hypertrophic type showed fair efficacy (100%), and no improvement was observed in patients of the nodular thickening type (100%). Pain, pruritus, and a burning sensation were observed during treatment. Edema was noted on the treated areas post-treatment. No other obvious systemic adverse reactions were observed. ConclusionHMME-PDT is an effective and safe treatment for adult patients with purple PWSs. Multiple HMME-PDT treatments can improve the response and cure rate.

Carbonylation induced by antibiotic and pesticide residues on casein increases its IgE binding and allergenicity

This work aimed to evaluate the effect of carbonylation induced by tetracyclines, β-lactams, fluoroquinolones, and pyrethroids in caseins of bovine origin on their immunoreactivity and allergenicity. Using a spectrophotometric method, ELISA, dot-blot, and an IgE-mediated milk allergy mouse model, we confirmed that antibiotics and pesticides at their maximum residue limit, promoted the in vitro carbonylation of caseins (among 5.0 ± 0.01 and 67.5 ± 0.70 nmol of carbonyl/mg of protein); furthermore, carbonylations greater than 19 nmol significantly increase the in vitro IgE immunoreactivity of caseins (average OD among 0.63–1.50) regarding the negative control (average OD: 0.56). On the other hand, sensitized mice exposed to oxidized caseins showed increased clinical scores (2–5), positive skin tests, and footpad swelling (0.28–0.59 mm) compared to the negative control (1–2; negative skin tests; 0.1 mm, respectively), denoting increased allergenicity. These results suggest that casein carbonylation increases their IgE immunoreactivity and allergenicity, a fact that could be explained by the resistance to the digestion promoted by carbonylation and by conformational changes in the random coil casein structure, which can expose cryptic epitopes or neoepitopes.

Comparative Assessment of Platinum Salts and Taxane Group Hypersensitivity Reactions, The Role of Skin Tests in Diagnosis?

We aimed to investigate the role of skin tests (ST) in the diagnosis of hypersensitivity reactions (HSRs) with platinum salts (PS) and taxane (TX) groups drugs and their reliability in patient management. Patients' data who developed immediate HSR with PS and TX were recorded and ST was performed. The gradual challenge was applied to all patients with ST negative and grade 1-2 with the suspect drug. In total, the data of 104 patients (74 with PS, 30 with TX) who developed HSR against PS and TX were shared. The gradual challenge was applied to 72 ST negative and grade 1-2 patients (46 PS group, 26 TX group). The gradual challenge was negative in 39 patients in the PS group and 23 patients in the Tx group. The negative predictive value (NPV) for PS was 83% and NPV for TX was 88%. We found significantly higher skin test positivity in patients with PS and TX and grade 3 HSR (p = 0.007, p = 0.001). A significant correlation was found between skin test positivity and early onset of symptoms (p = 0.001 for PS, p = 0.015 for TX). In terms of symptoms witnessed in HSR, we observed the itching, urticaria, hypotension, syncope, and abdominal pain symptoms significantly more in the group with a positive skin test (p < 0.024, p < 0.001, p < 0.001, p < 0.002, and p < 0.025, respectively). We found very high NPV values for PS and TX. We found that the gradual challenge applied to patients with negative skin tests is reliable if Grade 3 HSR is not observed and with this approach, unnecessary desensitization processes and/or drug alterations can be avoided.

M056 SUSPECTED OCRELIZUMAB-INDUCED IMMEDIATE HYPERSENSITIVITY: NEGATIVE SKIN TESTING AND DRUG PROVOCATION TEST

Ocrelizumab is a monoclonal antibody commonly used in the treatment of multiple sclerosis (MS). Hypersensitivity reactions to ocrelizumab have been reported in up to 5.6 % in non-African American patients. To date, non-irritating skin testing concentrations for ocrelizumab have not yet been established. We present a patient with negative skin testing (ST) and a negative drug provocation test (DPT) to ocrelizumab.

M010 DIAGNOSTIC CHALLENGE IN EVALUATING THE RISK AND MANAGEMENT OF ALLERGIC REACTION(S) TO SARS-COV-2 VACCINES

The frequency of immediate hypersensitivity reactions following immunization with either the Pfizer-BioNTech (BNT162b2) or Moderna (mRNA-1273) mRNA vaccines poses a clinical challenge for the allergist-immunologist. Anaphylaxis to the mRNA COVID-19 vaccines is currently estimated to occur in 2.5 to 11.1 cases per 1 million doses. Although excipients [polyethylene glycol (PEG), and polysorbate] and specific mRNA and Ad26.COV2.S components in COVID-19 vaccines have been cited as potential causative allergens, PEG is considered the likely culprit in mRNA vaccines. However, several skin testing published protocols using PEG have yielded conflicting results. We present a patient who developed anaphylaxis after the first dose of BNT 162b2 who was evaluated by PEG, polysorbate, and COVID-19 vaccine skin testing. A 49-year-old female, with a known atopic history, was evaluated for an anaphylactic reaction to BNT 162B2 vaccine occurring within 30 minutes after the first dose. Pruritic symptoms, facial urticaria, tongue swelling, and wheezing progressed to full body hives and difficulty breathing. Following treatment with epinephrine, IV diphenhydramine, and IV steroids, her symptoms improved. SPT and ID skin testing to PEG, polysorbate 80, and the BNT 162B2 and JNJ-78436735 (Johnson and Johnson) were negative except for positive ID testing to polysorbate 80. Negative SPT and ID skin testing with both excipients and vaccine specific components argues against an IgE-mediated mechanism and suggests a non-IgE mechanism. IgE skin testing may have no value as a predictive biomarker of susceptibility to allergic reactions of the mRNA COVID-19 vaccines and will require more research focused on non-IgE mechanisms.

75% negative skin test results in patients with suspected hypersensitivity to beta-lactam antibiotics: Influencing factors and interpretation of test results

BackgroundThe diagnostic approach for beta-lactam (BL) drug hypersensitivity reactions (DHR) is based on the history, clinical signs, skin tests (ST), in vitro tests, and drug provocation tests (DPT). The aim of this study was to assess the performance of an allergy workup with ST in a real-world use. MethodsIn this cross-sectional study the rate of positive ST in subjects with suspected DHR to penicillins and cephalosporins was investigated. Of special interest were correlations of ST positivity: 1) to the time intervals between index reaction and the allergic work-up, 2) time interval from drug exposure to the onset of signs, 3) pattern of manifestation in delayed DHR and involvement of test area in the index reaction, and 4) potential advantage of patch testing in delayed DHR. Results175 patients were included between January 2018 and April 2019 (63.4% female), 45 (25.7%) with immediate DHR manifestation and 130 with delayed DHR manifestation (74.3%). A total of 44 patients (25.1%) had a positive ST (immediate DHR 37.8% versus 20.0% in delayed DHR). ST positivity decreased in both groups after 3 years from 47.8% [95%CI 29.2–67] to 23.5% [95%CI 9.6–47.3] in immediate DHR and 23.0% [95%CI 15-4-32.9] to 12.9% [95%CI 5.1–28.9] in delayed DHR. The proportion of positive ST was higher in patients with more severe forms of delayed DHR, and in subjects with a shorter latency period of onset of symptoms after drug exposure: 0-3d: 29.5% [95%CI 19.6–41.9] vs. >3d: 11.6% [95%CI 6.0–21.2]). No sensitization was shown in delayed urticaria or angioedema. ST done outside the skin area involved during the index reaction were negative in all cases (0/38 vs. 26/84 in cases with involved area). The combination of patch test and intradermal test (IDT) revealed an additional positive result in 2/77 cases. Additional in vitro testing reduced the proportion of negative test results to 72%. ConclusionIn most patients with negative test results, we could not clarify the cause of the BL-associated adverse events even with further investigations (including DPT). How to prevent new drug-induced adverse events in such patients has hardly been investigated yet. Corresponding cohort studies could improve the data situation.

The Role of Skin Tests in the Prevention and Diagnosis of Hypersensitivity Reactions to Platinum Agents in Gynecological Cancer: A Single-Center Italian Retrospective Study.

Simple SummaryThe development of hypersensitivity reactions to platinum agents in patients with gynecological cancers limits the use of platinum re-treatment for recurrent disease. In those patients who developed a hypersensitivity reactions during treatment with platinum agents it could be safer to undergo allergy diagnosis. This approach includes the in-vivo skin tests before re-exposure to the platinum agent, especially in those patients who have to undergo a 2nd or 3rd line therapy. In our experience, skin test for platinum agents resulted in a simple and sensitive tool for the diagnosis and prevention of hypersensitivity reactions to platinum agents. In addition, this approach identified a sub-group of patients that became sensitized to the platinum agent during the previous platinum-based therapy. Background: Hypersensitivity reactions (HSR)s to platinum agents are increasing in frequency, due to their extensive use and repeated exposures in patients with increased life expectancy. The aims of our study are to analyze the frequency of both type I and type IV HSRs in patients with gynecological cancer treated with (CBDCA) carboplatin and/or (CDDP) cisplatin, to evaluate the role of skin tests in the diagnosis and prevention of HSRs. Methods: From 2011 to 2018, we evaluated 124 consecutive female patients previously treated with CBDCA and/or CDDP for gynecological cancer. All patients, including those with and without HSR to previous platinum-based therapy, underwent in-vivo skin tests for platinum agents before starting the second or more therapeutic lines. To reduce the risk of false negative results, patients with a negative skin test at the first evaluation were re-tested after 3 weeks from the platinum re-exposure. Results: Among the 124 patients evaluated, 58 (47%) experienced HSRs to at least one platinum agent: 35% were to CBDCA, 5% to CDDP, 7% to both. Fifty-six of the 58 HSRs were classified as immediate and two delayed. Skin tests confirmed an IgE-dependent mechanism in 67% of patients with immediate-HSRs to CBDCA and identified a cross-reactivity between platinum agents in 18% of patients. Moreover, among those who had never developed an HSRs during platinum-based therapy, in-vivo skin tests identified 12% of sensitized patients. Conclusions: On the basis of our findings, skin test for platinum agents is a simple and sensitive tool for the diagnosis and prevention of HSRs to CBDCA and/or CDDP and can be useful for detecting possible cross-reactivity among platinum agents.

MRNA COVID-19 vaccine safety in patients with previous immediate hypersensitivity to pegaspargase

mRNA COVID-19 vaccine safety in patients with previous immediate hypersensitivity to pegaspargase

Diagnostic Approach of Hypersensitivity Reactions to Cefazolin in a Large Prospective Cohort

Cefazolin is a common trigger of perioperative anaphylaxis. The diagnostic approach is controversial because the optimal concentration for skin testing is uncertain, drug provocation tests (DPTs) are contraindicated in severe reactions, and invitro tests are not thoroughly validated. We aimed to characterize a large number of patients reporting cefazolin allergic reactions and to analyze the diagnostic role of invivo and invitro tests. We prospectively evaluated patients with suspicion for allergic reactions to cefazolin by clinical history, skin tests (STs), and, if negative, DPT. In a subgroup of patients, basophil activation test (BAT) and radioallergosorbent test were done before allergologic workup was performed and the final diagnosis was achieved. We evaluated 184 patients, 76 of whom were confirmed as allergic (41.3%), 90 were nonallergic (48.9%), and 18 were nonconfirmed (9.8%). All patients reporting anaphylactic shock and most reporting anaphylaxis were confirmed to be allergic (P < .001). Forty allergic patients (52.6%) were confirmed by STs, 22 by DPT (28.9%), and 14 by clinical history (18.4%). All subjects manifesting exanthemas and pruritus were nonallergic. The BAT sensitivity was 66.7% when CD63 and CD203c were combined as activation markers. Six of 8 patients with negative STs and positive DPT had a positive BAT. Patients allergic to cefazolin often reported severe immediate-type reactions. Skin tests enabled a diagnosis in half of patients when using cefazolin at 20 mg/mL. Unfortunately, DPT could not be performed in all patients owing to reaction severity, which makes BAT a promising diagnostic tool. Further research is needed to clarify the underlying mechanisms, especially in severe reactions.

The Role of Skin Tests and Premedication in Radiocontrast Media Hypersensitivity: A Clinical Dilemma

ABSTRACT Objective: Controversies continue over the diagnostic approach, prediction, and premedication in radiocontrast media (RCM) hypersensitivity. One of the most important problems encountered in daily clinical practice is that patients do not recall which contrast agent has been used in previous exposures. Also, in most cases, the details of the reaction have not been recorded. Therefore, difficulties are experienced in decision-making about skin testing and premedication in patients who are suspected of RCM hypersensitivity. To assess the clinical value of skin tests and premedication in RCM hypersensitivity. Materials and Methods: A retrospective evaluation was made of the medical records of patients between October 2014 and December 2019. The skin tests were performed with the culprit agent if it was known, otherwise, with iohexol, one of the most commonly used RCM in Turkey. As premedication, oral methylprednisolone 40 mg 13-7-1 hours before the procedure and oral pheniramine 22.7 mg 1 hour before the procedure were prescribed. Results: A total of 41 patients were evaluated (32 females and 9 males). Of the reactions, 35 (85.4%) were immediate and 6 (14.6%) were non-immediate. Three (7.3%) had a positive intradermal test result. It was determined that 20 patients (17 immediate, 3 non- immediate), required imaging with RCM again. Of these, 18 received premedication and two did not, although it was recommended. Of the patients who received premedication, one (5.5%) had an urticarial reaction of the same grade, while both patients (100%) who did not receive premedication developed an immediate allergic reaction that was of a similar grade to that of the previous reaction. Conclusion: Skin test positivity for RCM was observed at low rates. In cases with negative skin tests and when the culprit drug cannot be identified, re-exposure to alternative RCM under premedication may reduce the risk of the reaction. Keywords: Allergy, iodinated contrast media, iobitridol, iohexol, premedication

Interleukine-22 gene variants are associated with susceptibility to visceral leishmaniasis

Visceral leishmaniasis (VL) is an infectious disease caused by an intracellular protozoan belonging to Leishmania species. Interleukin (IL)-22 plays an important role in inflammatory response, chemotaxis, regulation of cellular proliferation and tissue repair. Considering the role of IL-22 in control of leishmaniasis and the effect of its single nucleotide polymorphisms (SNPs) on respective function and production, this study aimed to investigate the probable association of IL-22 SNPs with VL. The study was carried out on 110 patients with VL, 102 healthy individuals with negative leishmanin skin test (negative control group (NCG)), and 144 healthy individuals with positive leishmanin skin test (LSTPG). Four SNPs in IL-22 including rs2227501, rs2227503, rs2227513 and rs1026786 were analyzed by polymerase chain reaction-restricted fragment length polymorphism (PCR– RFLP) in the study groups. The frequency of A allele and AA genotype at rs1026786 were significantly higher in the LSTPG group than in the patients (P = 0.013 and P = 0.001, respectively). Conversely, the frequency of AG genotype was significantly higher in the patients and the NCG than in the LSTPG group (P = 0.0001 and P = 0.002, respectively). For rs2227503, the frequency of AG genotype was significantly higher in the LSTPG group than in the NCG (P = 0.025). The haplotype TGAA frequency was significantly higher in the NCG, compared to patients and LSTPG group (P = 0.004 and P = 0.023, respectively). The frequencies of haplotypes TAAG and TGAG were significantly higher in the patients than in the LSTPG group (P = 0.046 and P = 0.014, respectively). The TAAA/TAAG frequency was significantly higher in the patients than in the LSTPG group (P = 0.013). Inheritance of rs1026786 A allele and AA genotype of IL-22 could be a possible protective factor against VL, whereas the inheritance of the haplotypes TAAG and TGAG may predispose Iranian population to the disease.

Algorithm to guide re-exposure to penicillin in allergic pregnant women with syphilis: Efficacy and safety

BackgroundGestational syphilis is underdiagnosed and undertreated, leading to stillbirth, prematurity, low birthweight, neonatal death, and congenital syphilis. Most patients who label as allergic to penicillin are misdiagnosed. ObjectiveTo assess the efficacy and safety of an algorithm to guide re-exposure to penicillin in pregnant women with syphilis and reporting allergy to the antibiotic. MethodsWe performed a prospective study assessing pregnant women with syphilis and labeled as allergic to penicillin. Based on clinical history, patients were divided in two groups: high-risk and low-risk to penicillin allergy. Low-risk patients with negative skin testing and negative serum specific IgE to penicillin underwent drug provocation test. The remaining patients underwent desensitization. ResultsNinety-one patients were enrolled. Allergy to penicillin was confirmed in 7.69% of pregnant women with syphilis and clinical history of allergy to penicillin; in all cases the diagnosis was made through intradermal testing, which predicted 100% of the breakthrough reactions observed during rapid drug desensitization (p < 0.001). Risk stratification based on the initial clinical reaction and skin testing to guide penicillin re-introduction through drug challenge or desensitization was safe (97.8%) and effective (97.8%). ConclusionWe developed and showed the efficacy and safety of an algorithm to guide re-exposure to penicillin in pregnant women with syphilis and labeled as allergic to this drug. Intradermal test is an excellent biomarker in the diagnosis of immediate hypersensitivity reaction to penicillin and to predict breakthrough reaction during rapid drug desensitization. Further studies may confirm the greater safety of the intravenous protocol compared to the oral protocol.

Betalactam hypersensitivity: The importance of delabelling in primary care

An allergy work-up was performed on adult patients with a history of a penicillin allergy seen by primary medical care in Monastir (Tunisia) between July 2016 and February 2018. Patients with negative skin tests were challenged with amoxicillin. Patients who were delabelled were contacted by phone after 6months to determine outcomes after any therapeutic penicillin-class antibiotic intake. A total of 39 patients were evaluated and 33 (84.6%) were delabelled. Five patients were penicillin skin-test positive and one was oral challenge positive. We succeeded in contacting 33 delabelled patients at 6months. Twenty-two patients tolerated a subsequent therapeutic course of amoxicillin, eight patients did not retake penicillin due to a lack of therapeutic indication, and three patients refused an indicated penicillin use fearful of another reaction. This study highlights the importance of allergy work-up in the diagnosis of beta-lactam hypersensitivity. Most patients were excessively labelled as beta-lactam allergic and this mislabelling could increase healthcare costs and lead to the development of drug resistance by the use of wide-spectrum antibiotics.

Value of skin tests for managing allergic hypersensitivity reactions to platinum compounds.

Background Platinum-based therapy continues to be one of the pillars of the treatment of different types of cancer. However, many times the responsible clinician renounces its use after the appearance of a hypersensitivity reaction. Objective To assess the value of skin tests (ST) in clinical practice to address the treatment of patients with suspicion of immediate hypersensitivity reactions (HSRs) to platinum compounds. Method Single-center retrospective study of 3years. Adult patients treated with any platinum compound who experienced HSR symptoms and for whom an oncologist requested ST, were included. ST with cisplatin, carboplatin and oxaliplatin were performed. Results Twenty-two patients were included. ST were positive in 12 patients (54.5%), of which 4 (33%) presented cross-reactivity to another platinum compound. Fifteen patients continued platinum-based chemotherapy: 9 patients with positive ST (4 continued by desensitization and 5 with another platinum compound) and 6 patients with negative ST, of which 1 repeated an HSR. A NPV of 0.91 was calculated. Conclusion ST helped physicians identify patients most susceptible to platinum derivative allergies and resume platinum-based therapy in many patients for whom no suitable therapeutic alternative was clinically acceptable.

Hypersensibilités aux produits de contraste iodés : analyse en cluster

Introduction Cluster analysis refers to a broad set of unsupervised learning techniques used to discover distinct subgroups or clusters within a set of data. This study aimed to distinguish different clinical characteristics among patients with suspicions of drug hypersensitivity reactions (DHRs) to iodinated radiocontrast media (iRCM) based on a cluster analysis. Methodes A retrospective study was performed using data extraction from the Drug Allergy and Hypersensitivity Database (DAHD) at the Allergy Unit, University Hospital of Montpellier, France. All referred patients with suspicions of iRCM DHRs between February 2001 and December 2019 either with confirmed positive skin tests (ST)s or negative STs were included in the analysis. Resultats A total of 1439 patients with suspicion of a DHR to iRCM who underwent a drug allergy work-up were analysed. Positive STs were displayed in 153 patients (10.6 %). The solution proposed by the automatic cluster analysis categorized the 1439 patients into five clusters, with a fair quality of clustering and an optimal ratio (2.3) of the cluster sizes. Cluster 1 contained almost only patients with a non-immediate reaction. Cluster 2 comprised virtually only patients with immediate reactions (IR), all with known culprit iRCM. These were the best defined clusters. Cluster 4 and 5 were virtually identical, with one exception, namely the clinical manifestation. Where they both comprised IRs, with multiple episodes of DHR, induced by unknown culprits, tested two decades after the index reaction, cluster 5 contained virtually only anaphylactic events whereas cluster 4 included various reactions, but no anaphylaxis. Confirmed allergies were more frequent in cluster 1 (16.9 %) and 2 (16.5 %). Conclusion Five clinical phenotypes which make sense clinically were determined by cluster analysis. From a pragmatic point of view, this new knowledge can be integrated in the drug allergy work-up reasoning : patients with well-defined recent reactions are allergic in up to 17 % of cases, but the frequency of allergy is leveled down by two or more in reactions tested more than a decade after their occurrence, despite the clinical manifestation which can resemble anaphylaxis.