PEGylated liposomes for diagnosis of polyethylene glycol allergy.

BACKGROUND: Polyethylene glycol (PEG) is a nonprotein polymer that is present in its native (unbound) form as an excipient in a range of products. It is increasingly being utilized clinically in the form of PEGylated liposomal medications and vaccines. PEG is the cause of anaphylaxis in a small percentage of drug reactions; however, diagnosis of PEG allergy is complicated by the variable and poor diagnostic performance of current skin testing protocols. OBJECTIVE: We assessed the diagnostic performance of PEGylated lipid medications as an alternative to currently described tests that use medications containing PEG excipients. METHODS: Nine patients with a strong history of PEG allergy were evaluated by skin testing with a panel of PEG-containing medications and with a PEGylated lipid nanoparticle vaccine (BNT162b2). Reactivity of basophils to unbound and liposomal PEG was assessed ex vivo, and specificity of basophil responses to PEGylated liposomes was investigated with a competitive inhibition assay. More detailed information is provided in this article's Methods section in the Online Repository available at www.jacionline.org. RESULTS: Despite compelling histories of anaphylaxis to PEG-containing medications, only 2 (22%) of 9 patients were skin test positive for purified PEG or their index reaction-indicated PEG-containing compound. Conversely, all 9 patients were skin test positive or basophil activation test positive to PEGylated liposomal BNT162b2 vaccine. Concordantly, PEGylated liposomal drugs (BNT162b2 vaccine and PEGylated liposomal doxorubicin), but not purified PEG2000, consistently induced basophil activation ex vivo in patients with PEG allergy but not in nonallergic controls. Basophil reactivity to PEGylated nanoparticles competitively inhibited by preincubation of basophils with native PEG2000. CONCLUSION: Presentation of PEG on the surface of a lipid nanoparticle increases its in vivo and ex vivo allergenicity, and improves diagnosis of PEG allergy.

Outcomes of Serum Food-Specific Immunoglobulin G 4 to Guide Elimination Diet in Patients With Eosinophilic Esophagitis.

INTRODUCTION: Eosinophilic esophagitis (EoE) is associated with atopy; however, recent studies have identified an association with food-specific immunoglobulin G 4 (FS-IgG 4 ) rather than immunoglobulin E antibodies. This study aimed to evaluate the role of serum FS-IgG 4 in guiding an elimination diet and its outcomes. METHODS: Patients with and without EoE were enrolled in a prospective, controlled, single tertiary center trial. Serum FS-IgG 4 titers, esophageal eosinophil counts, and dysphagia symptom questionnaire scores were assessed, and participants with elevated FS-IgG 4 (ImmunoCAP, cutoff of 10 mgA/L) commenced 6-week targeted elimination diet. Repeat serum FS-IgG 4 and endoscopic and histologic examination were performed at 6-week follow-up. RESULTS: Twenty-two patients with active EoE and 13 controls were recruited. Serum FS-IgG 4 to milk, wheat, soy, eggs, and nuts was significantly higher in EoE ( P = 0.0002, P = 0.002, P = 0.003, P = 0.012, and P < 0.001, respectively). Elevated serum FS-IgG 4 to 1 or more food groups (median 2) was identified in 21/22 (95.4%) patients with EoE; 20/21 underwent 6-week dietary elimination. Median reductions in dysphagia symptom questionnaire score and EoE endoscopic reference score after elimination were 8 ( P = 0.0007) and 1 ( P = 0.002), respectively. Nine (45%) patients had histological remission (<15 eosinophils per high-power field). Fall in median esophageal eosinophil count was not statistically significant (50 vs 23; P = 0.068). Serum FS-IgG 4 did not decline by 6-week follow-up. DISCUSSION: Serum FS-IgG 4 to milk, wheat, soy, egg, and nuts was present at higher levels in EoE, with targeted elimination resulting in 45% histologic remission rate. Serum FS-IgG 4 has potential as a noninvasive biomarker in EoE. When successful, FS-IgG 4 -led elimination diet can negate need for medications and be viewed more favorably by patients because of its smaller endoscopic burden compared with empirical elimination diets.

The role of major and minor determinants in penicillin allergy testing: Time to revisit an old friend?

Background: Skin testing is an important step in evaluation of penicillin allergic reactions. It includes testing to the following: amoxicillin, benzyl penicillin, and products generated in vivo after penicillin administration, the major determinant hapten penicilloyl-polylysine (PPL) and the minor determinant mixture (MDM). Although PPL and MDM are available as a commercial kit, their supply and cost remain problematic. Objective: We aimed to evaluate the performance and utility of PPL and MDM in penicillin allergy testing. Methods: A retrospective audit over a 5-year period was undertaken for those with penicillin testing in a tertiary immunology unit. Results: In all, 214 patients were identified. Of those patients, 151 (70.6%) were female and the average age was 58 years. Unspecified penicillin was the most common index drug (n = 127 [59.3%]), followed by amoxicillin (n =3 [24.8%]) and amoxicillin-clavulanic acid (n = 21 [9.7%]). The result of skin testing was positive in 23 patients (10.7%); skin prick testing was positive in 10 patients (4.7%), and intradermal testing (IDT) was positive in 13 patients (6.1%), the majority of whom had identified amoxicillin or amoxicillin-clavulanic acid as the index drug (n = 22 [95.7%]). The result of testing to PPL and/or MDM was positive with IDT only (n=5 [23.8%]). PPL and MDM positivity coexisted with a positive reaction to amoxicillin IDT in 2 patients, 1 of whom passed an amoxicillin challenge. Additionally, 2 positive tests to PPL were present with a negative result for MDM; of these 2 positive results, 1 was positive to amoxicillin IDT. In only 1 case were the results of testing for MDM and PPL both positive, with negative results to all native ß-lactams tested; the patient tolerated an amoxicillin challenge. Overall, the negative predictive value for both skin prick testing and IDT was 89.5%. Conclusion: Benzyl penicillin and amoxicillin alone may be sufficient for in vivo testing in suspected individuals with penicillin allergy.

Lenalidomide Desensitization for Delayed Cutaneous Reaction: A Case Series and Review of the Literature.

BACKGROUND: Lenalidomide is commonly used for treatment of multiple myeloma (MM) as well as other hematological disorders. Cutaneous adverse reactions occur frequently and withholding lenalidomide treatment may have implications for prognosis. OBJECTIVE: To evaluate the role of lenalidomide desensitization in patients with cutaneous adverse reactions. METHODS: A retrospective review of patients referred for lenalidomide desensitization between May 2019 and May 2022 at a tertiary hospital. All patients underwent a 6-week outpatient desensitization with premedication. RESULTS: There were 12 patients: 10 males and 2 females with a median age of 65 years. All had MM with autologous stem cell transplantation and lenalidomide 10 mg daily added for maintenance therapy. Most patients (n = 8) had a generalized maculopapular exanthem with or without pruritus. All patients had delayed cutaneous reactions; the median time to onset was 14 days (range 2-28 d). Six patients tolerated desensitization: 5 on the first attempt and 1 after 3 attempts and supplementary oral prednisolone. Four patients underwent multiple (≤3) attempts at desensitization owing to breakthrough symptoms. In patients who failed desensitization, recurrence of symptoms occurred variably, either early (within days), within weeks, or delayed by more than 1 month. CONCLUSIONS: Lenalidomide desensitization is worthwhile and allows continuation of treatment. In our MM cohort, lenalidomide desensitization was successful in only 50% of cases, including some cases in whom ongoing symptoms were mitigated by cotreatment with antihistamine.

COVID vaccination can be performed in patients with a history of allergic reactions to the vaccines or their components: experience from a specialist clinic in South Australia.

BACKGROUND: The development of vaccines against SARS-CoV2 has been a key public health response to the COVID-19 pandemic. However, since their introduction, there have been reports of anaphylactic reactions to vaccines in individuals with history of allergic reactions to other vaccines, excipients or to COVID vaccines. AIM: A dedicated adult COVID vaccine allergy clinic with a standardised allergy testing protocol was set up to investigate safety and suitability of available COVID vaccines in Australia. METHODS: Patients referred to a state-wide COVID-19 vaccine allergy clinic between March and August 2021 with a history of allergy underwent skin-prick testing and intradermal testing to both available vaccine formulations (BNT162b2 and ChAdOx1-S), excipients (polyethylene glycol and polysorbate 80), excipient-containing medications and controls. Basophil activation testing was conducted in few subjects with convincing history of immediate type reactions. RESULTS: Fifty-three patients underwent testing for possible excipient allergy (n = 19), previous non-COVID vaccine reaction (n = 13) or previous reaction to dose 1 of COVID-19 vaccine (n = 21). Patients were predominantly female (n = 43, 81%), aged 18-83 (median 54) years. Forty-four patients tested negative and 42 of these received at least their first dose of a COVID-19 vaccine. Nine patients tested positive to excipients or excipient-containing medication only (n = 3), or vaccines (n = 6). Five patients were positive to just BNT162b2, 3/5 have been vaccinated with ChAdOx1-S. One who was skin test positive to both vaccines, but negative BAT to ChAdOx1-S was successfully vaccinated with ChAdOx1-S. CONCLUSION: Even in a high-risk population, most patients can be vaccinated with available COVID-19 vaccines. This paper reports local experiences using a combined allergy testing protocol with skin testing and BAT during the pandemic.

Real-world off-label use of icatibant for acute management of non-hereditary angioedema.

We retrospectively examined the indications and efficacy of off-label use of the bradykinin B2 receptor antagonist icatibant. The clinical heterogeneity, variability of response to icatibant and lack of efficacy of adrenaline described in this audit highlights both the need for biomarkers that can rapidly distinguish between histaminergic and non-histaminergic angioedema, and for guidelines to improve the utility of icatibant in the non-hereditary angioedema setting.

Anakinra desensitisation in patients with cryopyrin-associated periodic syndromes.

Cryopyrin-associated periodic syndrome (CAPS) is rare and patients experience rashes, arthralgias and fevers despite supportive treatment. In these cases, anakinra subcutaneous therapy is indicated which provides symptom control. However, adverse reactions notably injection-site related, are common resulting in treatment cessation in these patients. Ongoing symptoms lead to morbidity and predispose patients to complications such as amyloidosis. We describe our experience with anakinra desensitisation in two cases with CAPS who had injection-site related reactions. We also propose a 34-day outpatient desensitisation protocol.

Vogt-Koyanagi-Harada syndrome presenting with bilateral optic disc swelling and leptomeningeal enhancement.

Vogt-Koynagi-Harada (VKH) disease is a clinical syndrome with classical ocular and extraocular findings that is not uncommonly described in Asian, Middle-Eastern and South American populations. We describe a case of VKH in an elderly Polish-Australian distinguished by prominent bilateral disc swelling rather than uveitis and marked leptomeningeal enhancement on MRI which led to extensive investigation including brain biopsy. Both disc oedema and MRI abnormalities improved dramatically with systemic steroid therapy. VKH disease is an important differential to consider in older patients with an uveo-meningeal picture and atypical eye findings where other causes have been excluded.