Dear Editor, Interleukin (IL)-5 is a pivotal factor in eosinophilic inflammation. It promotes eosinophil hematopoiesis, chemotaxis, and activation. The role of IL-5 in the pathogenesis of ...eosinophilic asthma has been extensively studied and demonstrated in human subjects, as well in murine models. Humanized monoclonal antibodies against IL-5 (mepolizumab and reslizumab) and IL-5 receptor α-subunit (IL-5Rα; benralizumab) have recently been introduced for the treatment of severe eosinophilic asthma. A number of clinical trials have also evaluated the efficacy of IL-5-modulating agents in eosinophilic granulomatosis with polyangiitis (EGPA). Consequently, subcutaneous administration of mepolizumab is currently approved for use in severe asthma, as well as for EGPA. Likewise, benralizumab is indicated for severe and refractory eosinophilic asthma in adults, albeit not yet for EGPA. Eosinophilic disorders, other than asthma, that have also been evaluated for IL-5-modulating therapy include chronic eosinophilic pneumonia and hyper-eosinophilic syndrome.
The drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome represents a severe hypersensitivity reaction. Up-to-date treatment is based on withdrawal of medication, supportive care, ...and immunosuppression using high-dose corticosteroid (CS) therapy. However, evidence-based data are lacking regarding second-line therapy for steroid-resistant or steroid-dependent patients.
We hypothesize that the interleukin (IL)-5 axis plays a critical role in the pathophysiology of DRESS; hence, inhibition of this signaling pathway could offer a potential therapy for steroid-dependent and/or steroid-resistant cases, and it may offer an alternative to CS therapy in certain patients more prone to CS toxicity.
Herein, we collected worldwide data on DRESS cases treated with biological agents targeting the IL-5 axis. We reviewed all cases indexed in PubMed up to October 2022 and performed a total analysis including our center experience with two additional novel cases.
A review of the literature yielded 14 patients with DRESS who were treated with biological agents targeting the IL-5 axis as well as our two new cases. Reported patients are characterized by a female-to-male ratio of 1:1 and a mean age of 51.8 (17-87) years. The DRESS-inducing drugs, as expected from the prospective RegiSCAR study, were mostly antibiotics (7/16), as follows: vancomycin, trimethoprim-sulfamethoxazole, ciprofloxacin, piperacillin-tazobactam, and cefepime. DRESS patients were treated with anti-IL-5 agents (mepolizumab and reslizumab) or anti-IL-5 receptor (IL-5R) biologics (benralizumab). All patients have clinically improved under anti-IL-5/IL-5R biologics. Multiple doses of mepolizumab were needed to achieve clinical resolution, whereas a single dose of benralizumab was often sufficient. Relapse was noted in one patient receiving benralizumab treatment. One patient receiving benralizumab had a fatal outcome, although mortality was probably related to massive bleeding and cardiac arrest due to coronavirus disease 2019 (COVID-19) infection.
Current treatment guidelines for DRESS are based on case reports and expert opinion. Understanding the central role of eosinophils in DRESS pathogenicity emphasizes the need for future implementation of IL-5 axis blockade as steroid-sparing agents, potential therapy to steroid-resistant cases, and perhaps an alternative to CS treatment in certain DRESS patients more prone to CS toxicity.
Background
The mRNA-based COVID-19 vaccine was introduced to the general public in December 2020. Shortly thereafter, safety concerns were raised due to the reporting of allergic reactions. ...Allergy-related disorders were suspected to be significant risk factors and the excipient polyethylene glycol was suggested to be a robust allergen.
Methods
This is a retrospective study analysis. Subjects with putative risk factors for severe allergic reactions to the Pfizer-BioNTech BNT162b2 vaccine were referred for vaccination under observation at the Unit of Allergy and Clinical Immunology. Data was collected for each subject, including demographic details, medical history and previous reactions to any allergen. When appropriate, skin tests were done prior to vaccination.
Results
A total of 346 subjects received 623 vaccine doses under observation. The study included patients with various allergy-related disorders (n=290) and those with allergy to a previous COVID-19 vaccine dose (n=56). Both groups showed female predominance (78% and 88%, p=NS). Patients without reactions to previous doses reported more drug allergy (80% vs. 39%, p<0.001) and previous anaphylaxis (64% vs. 14%, p<0.001). There was no difference in sensitivity to other allergens, including polyethylene glycol. Under observation, mild allergic reactions were noted in 13 individuals characterized by female gender (100%), a history of anaphylaxis (69%) and drug allergy (62%). In 7 subjects, allergy was treated with antihistamines while others recovered spontaneously.
Conclusion
Our study demonstrates that vaccination under specialist-supervision is a powerful tool for reducing over-diagnosis of systemic reactions and for rapid and reliable collection of vaccine safety data.
The emerging COVID-19 pandemic poses many difficulties to medical professionals. One of them is the need to use personal protective equipment (PPE) in order to protect themselves and their families, ...while not compromising their care. Physical examination is one of the cornerstones of medical assessment but parts of it are nearly impossible to do while wearing protective equipment. In this brief report we demonstrate a novel wireless stethoscope and its use for treating suspected and proven COVID-19 patients, as a representative to other infectious diseases.
Highlights • HLH is a rare and potentially fatal auto-inflammatory condition, usually triggered by infection. • Controlling the infection while minimizing the auto-inflammatory response is ...challenging. • HSV-1 infection is a rare cause for fulminant hepatic failure and even rarer cause for HLH. • High index of suspicion and prompt diagnosis are crucial for successful treatment. • Early detection of fulminant viral infection by PCR is essential for diagnosis and treatment.
Background: Iodinated contrast media allergy is considered as a strong contra-indication for performing sialography. There is little evidence to support this approach. Objective: To evaluate the rate ...of iodinated contrast media (ICM) allergy in subjects undergoing sialography and to assess the risk for allergic responses in patients with a previous diagnosis of allergy. Methods: We retrospectively reviewed sialo-CBCT studies performed from 2014 to 2019. During the study period we implemented a protocol for performing sialo-CBCT in patients with a prior diagnosis of allergy: 1) Clinical data were collected from a questionnaire and medical records. 2) No premedication was administered but, instead, oxygen, epinephrine and a resuscitation cart were accessible. 3) Following the procedure, each patient was observed for one hour and contacted by telephone 24 hrs later. Results: No allergic responses were documented in the medical records of 1515 subjects following sialo-CBCT studies, including 13 individuals previously diagnosed with ICM allergy. Investigation of the subgroup with prior allergy disclosed that the range of injected volume was between 2 ml to 6.2 ml per patient and that complete secretion of ICM was detected in 7 of 13 patients. In the remainder of subjects, retention rates of 5-50% were observed. Conclusions: Allergic reactions are exceedingly rare following sialo-CBCT studies regardless of a previous diagnosis of allergy. Pre-medication with corticosteroids and antihistamines is usually not warranted.
BACKGROUNDIodinated contrast media allergy is considered as a strong contra-indication for performing sialography. There is little evidence to support this approach. OBJECTIVETo evaluate the rate of ...iodinated contrast media (ICM) allergy in subjects undergoing sialography and to assess the risk for allergic responses in patients with a previous diagnosis of allergy. METHODSWe retrospectively reviewed sialo-CBCT studies performed from 2014 to 2019. During the study period we implemented a protocol for performing sialo-CBCT in patients with a prior diagnosis of allergy: 1) Clinical data were collected from a questionnaire and medical records. 2) No premedication was administered but, instead, oxygen, epinephrine and a resuscitation cart were accessible. 3) Following the procedure, each patient was observed for one hour and contacted by telephone 24 hrs later. RESULTSNo allergic responses were documented in the medical records of 1515 subjects following sialo-CBCT studies, including 13 individuals previously diagnosed with ICM allergy. Investigation of the subgroup with prior allergy disclosed that the range of injected volume was between 2 ml to 6.2 ml per patient and that complete secretion of ICM was detected in 7 of 13 patients. In the remainder of subjects, retention rates of 5-50% were observed. CONCLUSIONSAllergic reactions are exceedingly rare following sialo-CBCT studies regardless of a previous diagnosis of allergy. Pre-medication with corticosteroids and antihistamines is usually not warranted.
Introduction and Objectives
Lenalidomide is considered a standard of care in multiple myeloma (MM) Some MM patients will develop delayed hypersensitivity to lenalidomide, which can lead to treatment ...discontinuation. Desensitization to lenalidomide can help these patients to complete treatment courses. Here, we aimed to review lenalidomide‐treated MM patients who developed delayed hypersensitivity‐induced rash and were treated with desensitization.
Methods
A retrospective analysis of medical files of MM patients, who were desensitized to lenalidomide due to delayed hypersensitivity rash. Patients were treated between 2018 and 2022 at Hadassah Medical Center, Jerusalem, Israel.
Results
Search of patients yielded 16 patients that underwent desensitization to lenalidomide within the study period. The desensitization protocol consisted of a slow, 3‐week‐long protocol with lenalidomide's target doses of 10, 15, and 25 mg/day. Of the 16 patients, 10 (62.5%) succeeded to complete the protocol and thus were able to complete lenalidomide treatment cycles. One patient with unsuccessful desensitization was subsequently treated with first‐generation IMiD thalidomide, with no rash appearing. None of the patients that were treated with desensitization had severe immune‐mediated or non‐dermatological adverse reactions.
Conclusions
Desensitization to lenalidomide is safe and effective. Discontinuation of lenalidomide in MM patients with delayed hypersensitivity and no contraindication to desensitization should be discouraged. Collaboration between hematologists and allergists is needed.
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