Delayed allergic reaction from bupropion in a 27-year-old male with MDD: A case report and literature review.

Introduction: Bupropion is an antidepressant approved for the treatment of major depressive disorder (MDD), seasonal affective disorder, and smoking cessation. Nausea, headache, tremor, and insomnia are well-known adverse effects of this medication. Less well-recognized adverse effects include delayed allergic reactions, which, in some cases, can appear 2 or more weeks after bupropion initiation. Case Report: A 27-year-old male with recurrent MDD was referred for medication treatment at an outpatient mental health clinic and prescribed bupropion XL. On day 28 of treatment, he reported significant improvement in depressive symptoms and the development of itchiness and urticaria on his extremities and back. Bupropion was tapered over the course of 7 days, and he was given cetirizine 10 mg daily. He was transitioned to venlafaxine treatment and experienced complete resolution of hives and pruritus. Discussion: Despite published reports on bupropion causing delayed hypersensitivity reactions, there remains limited clinical recognition of this side effect, and the risk of underrecognition may be greater when the onset of the reaction is more than 2 weeks after bupropion initiation. Conclusion: Bupropion can cause delayed hypersensitivity reactions, including delayed pruritis and urticaria. The risk may be highest in males aged 17 to 40 years and those with a history of allergic reactions.

A multicentre comparative cohort study of severe maculopapular exanthema and drug reaction with eosinophilia and systematic symptoms.

CLINICAL IMPLICATIONS: In a prospective cohort of antibiotic-associated delayed hypersensitivity reactions, key clinical characteristics and diagnostic discrepancies (in vivo and ex vivo) were noted between DRESS (RegiSCAR ≥4) patients and those with lower RegiSCAR scores (RegiSCAR 2-3) patients.

Ibuprofen: The Hidden Culprit Behind Aseptic Meningitis.

Drug-induced aseptic meningitis represents a significant clinical entity characterized by an inflammatory response of the meninges triggered by specific pharmacological agents. This condition predominantly manifests as a delayed hypersensitivity reaction to a variety of drugs, most notably non-steroidal anti-inflammatory drugs, antibiotics, immune checkpoint inhibitors, and monoclonal antibodies. We report a case of aseptic meningitis in a 54-year-old male presenting with nausea and blurred vision two hours after taking ibuprofen. This case aims to highlight one underrecognized adverse event associated with one of the most commonly used over-the-counter medications worldwide.

Bilateral purtscher-like retinopathy associated with DRESS syndrome: a case report.

BACKGROUND: To report a case of Bilateral Purtscher-like retinopathy associated with DRESS syndrome managed with ocular and systemic treatments. CASE PRESENTATION: A 29-year-old healthy female developed multi-organ (cutaneous, hematologic, renal and hepatic) disfunction and profound vision loss 1 month after Human papillomavirus vaccine injection. At the first presentation, her visual acuity was counting fingers in both eyes. Fundus exam showed remarkable cotton-wool spots, retinal hemorrhages and macular edema. She was diagnosed DRESS syndrome and Purtscher-like retinopathy and treated with intravitreal injection of ranibizumab, systemic steroids anticoagulants, and plasma exchange. The patient finally recovered from this life-threatening condition but left with permanent visual damage. CONCLUSION: Purtscher-like retinopathy could be complicated by DRESS syndrome which is usually considered a type IV hypersensitivity reaction.

Exploring recent advances in drugs severe cutaneous adverse reactions immunopathology.

Severe cutaneous adverse reactions to drugs (SCARs) are rare but life-threatening delayed allergies. While they primarily affect the skin, they can also affect internal organs. Accordingly, they present with diverse clinical symptoms that vary not only between SCARs subtypes but also among patients. Despite the availability of topical and systemic treatments, these only address the symptoms and not the cause. To develop more effective therapies, it is necessary to elucidate the complexity of the pathophysiology of SCARs in relation to their severity. In line with the new type IV hypersensitivity reactions nomenclature proposed by the European Academy of Allergy and Clinical Immunology (EAACI), this review highlights the current insights into the intricate immune mechanisms engaged, the interplay between the culprit drug and genetic predisposition in drug presentation mechanisms, but also how external factors, such as viruses, are implicated in SCARs. Their relevance to the development of targeted medicine is also discussed.

The Australasian Registry for Severe Cutaneous Adverse Reactions (AUS-SCAR) - Providing a roadmap for closing the diagnostic, patient, and healthcare gaps for a group of rare drug eruptions.

Background: Severe cutaneous adverse reactions (SCAR) are a group of delayed presumed T-cell mediated hypersensitivities associated with significant morbidity and mortality. Despite their shared global healthcare burden and impact, the clinical phenotypes, genomic predisposition, drug causality, and treatment outcomes may vary. We describe the establishment and results from the first Australasian registry for SCAR (AUS-SCAR), that via a collaborative network advances strategies for the prevention, diagnosis and treatment of SCAR. Methods: Prospective multi-center registry of SCAR in Australian adult and adolescents, with planned regional expansion. The registry collects externally verified phenotypic data drug causality, therapeutics and long-term patient outcomes. In addition, biorepository specimens and DNA are collected at participating sites. Results: we report on the first 100 patients enrolled in the AUS-SCAR database. DRESS (50%) is the most predominant phenotype followed by SJS/TEN (39%) and AGEP (10%), with median age of 52 years old (IQR 37.5, 66) with 1:1 male-to-female ratio. The median latency for all implicated drugs is highly variable but similar for DRESS (median 15 days IQR 5,25) and SJS/TEN (median 21 days, IQR 7,27), while lowest for AGEP (median 2.5 days, IQR 1,8). Antibiotics (54.5%) are more commonly listed as primary implicated drug compare with non-antibiotics agent (45.5%). Mortality rate at 90 days was highest in SJS/TEN at 23.1%, followed by DRESS (4%) and AGEP (0%). Conclusion: In the first prospective national phenotypic and biorepository of SCAR in the southern hemisphere we demonstrate notable differences to other reported registries; including DRESS-predominant phenotype, varied antibiotic causality and low overall mortality rate. This study also highlights the lack of standardised preventative pharmacogenomic measures and in vitro/in vivo diagnostic strategies to ascertain drug causality. Trial registration: ANZCTR ACTRN12619000241134. Registered 19 February 2019.

Temporary Delayed Hypersensitivity Reaction to Botulinum Toxin-A After COVID-19 Vaccination: A Case Series.

PURPOSE: The occurrence of a hypersensitivity reaction with the injection of botulinum toxin type A (BTX-A) in cosmetic use is a rare complication. We report the largest case series of temporary delayed hypersensitivity reaction (DHR) with BTX-A following COVID-19 vaccination and the first cases to incobotulinum toxin A (incoBTX-A). METHODS: A retrospective multicentric case series of patients who developed a DHR to BTX-A after COVID-19 vaccination. RESULTS: Twelve patients were treated with BTX-A injections for the management of facial rhytids. The age range was between 29 and 45 years. Ten (83.3%) were female. Ten (83.3%) patients received incoBTX-A, and two received onabotulinum toxin A (onaBTX-A). All patients had COVID-19 vaccination (mRNA vaccine) between 1 and 7 months before. Within an average time of 24 h after BTX-A injection, all patients developed progressive facial swelling and erythema that were more prominent at the injection points. Intradermal allergic tests to BTX-A were performed in six (50%) patients, and the results were all negative. Adequate clinical control was achieved with systemic corticosteroids and antihistamines. After 1 year with no further vaccination, a new BTX-A treatment (provocation test) was performed in all patients with no secondary effects. CONCLUSION: Previous COVID-19 vaccination and the absence of new adverse events with further BTX-A injections suggest a temporary DHR. Clinicians should be aware of the importance of immunization history and its potential post-vaccine immunogenic effects with BTX-A. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Cutaneous hypersensitivity to chlorhexidine following facial fat grafting: a delayed intradermal response.

Chlorhexidine (CHD) is commonly included in surgical antiseptics and can be associated with adverse reactions ranging from contact dermatitis to anaphylaxis. A 32-year-old female presented to the OR for facial fat grafting. Surgical sites were prepped with CHD gluconate or topical iodine. Donor and recipient sites were infiltrated with local anesthetic injection prior to fat harvest and facial injection. Eleven days later, she presented with new painful, pruritic rash over donor sites where CHD had been applied prior to local anesthetic infiltration. Treatment with topical clobetasol and prednisone taper resulted in complete symptom resolution. This patient's response most likely represented a delayed type IV, T-cell mediated hypersensitivity. CHD is a known trigger of allergic reactions. Infiltration of local anesthetic may introduce skin prep into the subcutaneous tissue akin to intradermal testing. For those with delayed cutaneous reactions, steroids may provide symptomatic relief.

Maculopapular rash with multiple drug hypersensitivity to cotrimoxazole, amikacin, piperacillin/tazobactam, and meropenem in a patient with hairy cell leukemia.

We describe a rare case of a 54-year-old female with hairy cell leukemia, who following treatment for neutropenic sepsis, developed an extensive severe maculopapular exanthema with perifollicular hemorrhage. Cladribine, cotrimoxazole, allopurinol, domperidone, amikacin, piperacillin/tazobactam, and meropenem had all been given in the 9 days prior to eruption onset. Three months later, drug patch testing/delayed intradermal testing was positive to cotrimoxazole, trimethoprim, amikacin, piperacillin/tazobactam, and meropenem, with additional evidence of penicillin cross-reactivity. Drug challenge tests were negative to allopurinol and domperidone. She was diagnosed with multiple drug hypersensitivity to cotrimoxazole, amikacin, piperacillin/tazobactam, and meropenem. Multiple drug hypersensitivity is a novel syndrome mainly seen with severe delayed type IV drug eruptions, involving long-lasting strong T-cell reactivity to two or more structurally unrelated drugs.

Nonepisodic angioedema with eosinophilia following a rose-thorn prick injury.

Background: Nonepisodic angioedema with eosinophilia (NEAE) is a condition marked by angioedema and significant eosinophilia and often linked with atopic dermatitis. It predominantly affects young Asian women and occurs more frequently in the autumn and winter. Despite over 100 reported cases, its etiology and pathogenesis remain unclear. Case presentation: A 23-year-old Japanese female florist presented with acute arm swelling following rose-thorn pricks to her hands and fingers in spring. One week later, she developed progressive symmetrical non-pitting edema in her lower legs and a 3 kg weight gain without any rash. She had a history of oral allergy syndrome to apples and pears for which allergen-specific IgE were previously detected. Blood tests showed significant eosinophilia (14,930 cells/µL) and elevated thymus and activation-regulated chemokine (TARC) levels (12,864 pg/mL). Thyroid disease, autoimmune disorders, and hematologic malignancies were ruled out. Normal cardiac markers and a whole-body computed tomography excluded visceral organ involvement. She was diagnosed with NEAE and treated with oral prednisolone, which resolved the edema within 10 days. Prednisolone was tapered gradually on an outpatient basis without recurrence. Conclusion: A review of the literature indicates that NEAE triggered by subcutaneous antigen exposure may not follow the typical age or seasonal patterns. Direct subcutaneous antigen exposure, including rose-thorn pricks, can trigger NEAE. Clinicians should consider NEAE in atypical presentations and thoroughly investigate preceding episodes.

Cystic fibrosis: desensitization in delayed hypersensitivity reactions to elexacaftor/tezacaftor/ivacaftor.

Background: Cystic fibrosis transmembrane conductance regulator modulators are the only available treatment for cystic fibrosis. Although elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) is well-tolerated, rash has been reported as very frequent. In severe rashes, ELX/TEZ/IVA withdrawal is necessary, leading to clinical deterioration. The objective of the study is to increment the experience of ELX/TEZ/IVA desensitization. Methods: Adult patients who developed a delayed hypersensitivity rash to ELX/TEZ/IVA between December 2021 and February 2023 and required withdrawal due to ineffective rescue medication were included. Skins test for ELX/TEZ/IVA and IVA were conducted to establish hypersensitivity mechanism. Balijepally ELX/TEZ/IVA desensitization protocol was selected. In cases where desensitization had to be discontinued due to rash, an extended desensitization was proposed. Clinical and health-related quality of life parameters were collected before ELX/TEZ/IVA and after desensitization. Results: 162 patients (81 women, 31.2 [23.8-42.5] years) started ELX/TEZ/IVA, developing rash 12 of them (7.4%, six women). Six patients (five women) required stopping ELX/TEZ/IVA and were selected for desensitization. Skin tests indicated delayed type-IV hypersensitivity in one patient. Two patients presented adequate tolerance to desensitization; while, four patients developed rash. Three of these patients, successfully concluded extended desensitization (one patient declined participation). No significant clinical deterioration or quality of life worsening was observed during desensitization; in fact, there was an improvement in practically all mesured parameters. All five patients who resumed ELX/TEZ/IVA are currently receiving therapy with good tolerance. Conclusion: Desensitization to ELX/TEZ/IVA could be a successful and safe strategy for reintroducing this essential treatment in cases of a delayed hypersensitivity rash.

Delayed Type Hypersensitivity Reaction Induced By Liraglutide With Tolerance to Semaglutide.

Liraglutide is a glucagon-like peptide-1 (GLP-1) receptor agonist used for the management of type 2 diabetes and obesity. It was the first GLP-1 receptor agonist to be approved by the US Food and Drug Administration and the European Medicines Agency for the treatment of obesity. To date, numerous skin adverse reactions to liraglutide have been reported, but data regarding hypersensitivity reactions are scarce, raising concerns about its safety and clinical management. We present the case of a 56-year-old female patient with class 3 obesity who was started on subcutaneous liraglutide (Saxenda) by her endocrinologist. One month after starting the aforementioned treatment, the patient presented well-defined, round, erythematous pruriginous plaques surrounding the injection site, around 24 hours after the drug administration. A liraglutide-induced, delayed-type hypersensitivity reaction was suspected, which could be subsequently confirmed by allergy testing and histopathological study. This paper explores the clinical use of liraglutide, the occurrence of hypersensitivity reactions, diagnosis, management, and implications for future research. Understanding and managing liraglutide hypersensitivity is crucial to ensuring the safety and efficacy of this medication.

Surgically-Induced Necrotizing Scleritis After Pars Plana Vitrectomy: A Case Report.

Surgically induced necrotizing scleritis (SINS) is a rare delayed hypersensitivity reaction following ocular surgeries, characterized by pain and redness at the surgical site. While commonly reported in various ocular surgeries, its occurrence after vitreoretinal procedures remains infrequent. We present a case of a 61-year-old diabetic male who developed progressive scleral melting and uveal exposure two months after an uneventful 23-gauge vitrectomy for retinal detachment. The infectious and immunologic profile was negative. Despite aggressive medical and surgical interventions, the patient exhibited advancing scleral melting. The diagnostic challenge lies in determining the relative contributions of trauma, epithelial breakdown, immune activation, and infection in these patients. Our patient's uncontrolled diabetes potentially aggravated vascular disruption, contributing to delayed wound healing and immune complex deposition. The treatment involved topical steroids with broad-spectrum antibiotics, followed by conjunctival flap and oral corticosteroids. This case underscores the importance of early diagnosis, cautious immunosuppression, and thorough infection evaluation in managing postoperative scleritis. The limitations include a single culture test and the patient being lost to follow-up.

Glutaraldehyde-Induced Allergic Contact Dermatitis: A Case Report and Safety Standards.

Glutaraldehyde (GA), a potent disinfectant and sterilizing agent extensively used in healthcare settings, has garnered attention for its association with contact dermatitis. This occupational skin condition, often induced by repeated exposure to GA, poses significant challenges to the well-being of healthcare professionals and patients alike. Understanding the causes, symptoms, and preventive measures against GA-induced contact dermatitis is essential for promoting a safe and healthy working environment in healthcare facilities. A 28-year-old female presented with a severe burning sensation and dark brown patches in the lower chin region, one day following root canal treatment. Based on the characteristic appearance of patches and the typical burning sensation associated with an allergic reaction, a diagnosis of acute contact dermatitis was made. Patch testing by an expert dermatologist confirmed that the patient was allergic to GA. GA, a popular commercial germicidal product, is widely used as a cold sterilizing agent for operative dental instruments. The patient developed a reaction as the endodontic files used during the root canal procedure were cold sterilized with 2% GA. The lesion experienced significant improvement and ultimately healed following the administration of corticosteroids and antihistamines. This report concerns a case of GA-induced contact dermatitis. As GA is being used more widely, particularly in dental clinics, this case was of interest and is reported in the safety interest of patients and clinicians.

Contact allergy in Swedish professional ice hockey players.

BACKGROUND: Professional ice hockey players may contract irritant and allergic contact dermatitis. AIMS: To investigate the presence of contact allergy (CA) in professional ice hockey players in Sweden. METHODS: Ten teams from the two top leagues were assessed for potential occupational exposure to sensitizers. Exactly 107 players were patch tested with an extended baseline series and a working series, in total 74 test preparations. The CA rates were compared between the ice hockey players and controls from the general population and dermatitis patients. RESULTS: One out of 4 players had at least one contact allergy. The most common sensitizers were Amerchol L 101, nickel and oxidized limonene. CA was as common in the ice hockey players as in dermatitis patients and significantly more common than in the general population. Fragrances and combined sensitizers in cosmetic products (fragrances + preservatives + emulsifier) were significantly more common in ice hockey players compared with the general population. CONCLUSION: The possible relationship between CA to fragrances and cosmetic products on the one hand and the presence of dermatitis on the other should be explored further.