Balancing Benefits and Risks: A Literature Review on Hypersensitivity Reactions to Human G-CSF (Granulocyte Colony-Stimulating Factor).

Human granulocyte colony-stimulating factor (G-CSF) is a granulopoietic growth factor used in the treatment of neutropenia following chemotherapy, myeloablative treatment, or healthy donors preparing for allogeneic transplantation. Few hypersensitivity reactions (HRs) have been reported, and its true prevalence is unknown. We aimed to systematically characterize G-CSF-induced HRs while including a comprehensive list of adverse reactions. We reviewed articles published before January 2024 by searching in the PubMed, Embase, Cochrane Library, and Web of Science databases using a combination of the keywords listed, selected the ones needed, and extracted relevant data. The search resulted in 68 entries, 17 relevant to our study and 7 others found from manually searching bibliographic sources. A total of 40 cases of G-CSF-induced HR were described and classified as immediate (29) or delayed (11). Immediate ones were mostly caused by filgrastim (13 minimum), with at least 9 being grade 5 on the WAO anaphylaxis scale. Delayed reactions were mostly maculopapular exanthemas and allowed for the continuation of G-CSF. Reactions after first exposure frequently appeared and were present in at least 11 of the 40 cases. Only five desensitization protocols have been found concerning the topic at hand in the analyzed data. We believe this study brings to light the research interest in this topic that could benefit from further exploration, and propose regular updating to include the most recently published evidence.

Successful Dabrafenib Desensitization Protocols in a Patient with Metastatic Melanoma.

Dabrafenib and trametinib are two available molecules that have been approved for the treatment of metastatic melanoma with BRAF-V600E or V600K mutations. Their combined therapy has led to long-lasting survival benefits and substantially improved outcomes. Until now, only a few cases of severe hypersensitivity reactions to dabrafenib and vemurafenib have been reported, and even fewer desensitization protocols to these molecules have been documented. We report the case of a 71-year-old female patient with metastatic melanoma harboring a BRAF-V600E mutation undergoing targeted therapy with dabrafenib and trametinib. Two weeks after the initiation of the combined treatment, she developed a hypersensitivity reaction. The cause-effect relationship between dabrafenib and the hypersensitivity reaction was demonstrated twice, when symptoms recurred upon dabrafenib reintroduction. We started a rapid 3-day dabrafenib desensitization protocol, which was well tolerated. When the patient discontinued the drug administration, we decided on a longer protocol that included more steps and more days in order to prevent the occurrence of other hypersensitivity reactions. Our patient tolerated both rapid and slow-going schedules, the first one reaching the final dose within 3 days and the second one reaching the total daily dose within 14 days. Depending on the patient's needs, the severity of the hypersensitivity reaction and the hospital's availability, the doctor may choose either the rapid or slow-going desensitization protocol.

Contact Allergy Induced by Mango (Mangifera indica): A Relevant Topic?

INTRODUCTION: The most common clinical manifestation of mango allergy is contact dermatitis, which can be localized or systemic. The sensitising substances that have long been suspected are alk(en)yl catechols and/or alk(en)yl resorcinols. METHODS: We reviewed the original articles published on Pubmed, Embase and Cochrane Library before 15 September 2021, on the topic of contact allergy induced by mango and we synthesized the key data. RESULTS: We found 12 case reports and four case series, with a total of 37 patients. Only seven of these cases were reported in patients from mango-cultivating countries, the other 30 were from countries where mango cultivation does not occur, and 26 were also from countries where poison ivy/oak are commonly found. We found that contact dermatitis may occur on the first exposure to mango due to previous sensitisation to urushiol-containing plants. The diagnosis was confirmed by patch testing in some of the cases. There was great heterogeneity between the reagents used. CONCLUSION: Mango fruit is frequently consumed, but mango induced contact dermatitis, the main hypersensitivity reaction induced by mango, is rare. Further data is necessary for a better understanding of sensitising substances and, consecutively, standardization of patch test reagents.

Hypersensitivity reactions to nonsteroidal anti-inflammatory drugs: does age matter?

BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) are reported to be the leading cause of drug hypersensitivity reactions. The aim of this study was to characterize a cohort of patients with NSAID hypersensitivity and establish if there are any differences between two groups of adult patients, under 55 years old and over 55 years old, and identify safe alternative options. METHODS: Patients with NSAID hypersensitivity who were referred to a single tertiary Allergy center from January 2019 to December 2021 were included. Clinical information was obtained from a review of medical records. RESULTS: A total of 135 patients with a history of NSAID-induced hypersensitivity reactions were included, 80 patients under 55 years old and 55 patients older than 55. Most of the patients enrolled were female (80.74%) and the mean age was 50.21 years, ranging from 18 to 78 years old. The time interval between the first reaction and the allergy work-up was longer in the older group (average timeframe 6.87 years) than in the younger group (average timeframe 3.77 years). The main culprit was metamizole in both groups. An oral provocation test to paracetamol was performed in most of the patients who tolerated the intake of 1000 mg, except for 2 patients who developed angioedema. CONCLUSION: Angioedema was the most encountered symptom in our population. Age does not influence the allergy work-up of patients with a history of NSAID-induced hypersensitivity reactions. The drug provocation challenge remains the gold standard for finding a suitable alternative in patients with NSAID-induced hypersensitivity.

Drug Provocation Testing in the Diagnosis of Symmetrical Drug-Related Intertriginous and Flexural Exanthema (SDRIFE) Induced by Clarithromycin.

Introduction: Hypersensitivity reactions to macrolides are rarely described in the literature wherefore they are considered one of the safest choices for antibiotic treatment. Out of the reported reactions, cutaneous manifestations have the highest frequency, particularly non-immediate ones. Materials and methods: We report a case of a 71-year-old female who was referred to us for the drug allergy work-up of a rash unaccompanied by systemic signs, compatible with symmetrical drug-related intertriginous and flexural exanthema (SDRIFE) induced by clarithromycin. Results: The diagnosis was confirmed by a drug provocation test, which reproduced the index reaction. Discussion: As SDRIFE is quite infrequent, it can easily be misdiagnosed if the patient cannot present a clear history of the index reaction or the causal connection with the incriminated drug is not clear. Despite the fact that macrolides rarely induce hypersensitivity reactions, they must not be overlooked in the assessment of a drug induced reaction, as they are a potential etiological factor.

Omalizumab for successful chemotherapy desensitisation: What we know so far.

BACKGROUND: Hypersensitivity reactions induced by chemotherapeutic drugs may influence the course of the oncologic disease by preventing doctors from prescribing first-line therapy. In order to prevent another hypersensitivity reaction to the culprit chemotherapeutic agent, the physician can decide between two possibilities: premedication or desensitisation protocols. Rapid drug desensitisation showed successful results for most patients, but some of them may develop symptoms. Although omalizumab is not licensed as premedication or adjuvant therapy in chemotherapy desensitisation protocols, there have been published some case reports and small sample size studies that indicated promising results. METHODS: We reviewed all the published literature regarding the use of omalizumab during chemotherapy desensitisation protocols. RESULTS AND CONCLUSIONS: We found a great heterogeneity between the doses and the interval between omalizumab injections and chemotherapy - rapid drug desensitisation, but most of the studies showed promising results. As a corollary, we propose a dose regimen of omalizumab administered before the first desensitisation protocol. Then, omalizumab should be administered one day before every chemotherapy regimen. Omalizumab might be used as an adjuvant therapy and might be a solution for a hopeless situation.

Probiotics and prebiotics in atopic dermatitis: Pros and cons (Review).

Atopic dermatitis (AD) represents a chronic inflammatory skin condition in which the skin barrier is impaired; thus, the permeability is increased. Hence, there is a greater risk of allergic sensitization, as well as a higher pH and lower protection against resident microbes. Since this condition is currently increasing among children, it requires further study, as little is known regarding the pathogenesis that makes the skin prone to chronic relapsing inflammation. Trying to standardize the data regarding the use of prebiotics and probiotics in AD, we encountered tremendous variability in the literature data. Literature abounds in conflicting data: studies regarding prophylactic and therapeutic applications, different types of strains and dosages, applications in young children up to 5 years of age and above, usage of probiotics alone, prebiotics alone or synbiotics combined. There are also conflicting data regarding the outcome of these studies; some confirming a positive effect of prebiotics, probiotics or synbiotics and some showing no efficacy at all. The articles were divided into those assessing probiotics or prebiotics alone and a combination of the two, with studies showing a positive effect and studies proving no efficacy at all. We tried to critically analyze those articles showing weak and strong points. In summary, the most studied probiotics were the strains of Lactobacilli and Bifidobacteria. The Severity Scoring of Atopic Dermatitis (SCORAD) index was used to measure the efficacy of the treatment. Most studies compared their results with a placebo group and the efficacy when seen in moderate to severe forms of AD in patients with other allergic diseases present. However, the results are difficult to interpret, as in many studies the authors suggest that the disease may have a tendency to improve in time in some groups of patients.

Mite allergy and atopic dermatitis: Is there a clear link? (Review).

Atopic dermatitis (AD) represents a widespread chronic skin disease associated with different atopic disorders and allergies. These associations, similar to overall AD pathophysiology, are entangled, multifactorial and they are yet to be clarified. IgE and non IgE mediated pathomechanisms appear to be implicated in AD. Allergens constitute key aspects in AD pathogenesis, as they may serve as trigger factors. This review emphasizes mainly house dust mites (HDM), as they are likely the most relevant airborne allergen for AD. Here we review in a concise form the mite allergens, the role of molecular diagnosis and the treatment strategies for HDM. Strategies of avoiding allergens, with a few exceptions, are not enough to control children's AD; recent studies show HDM avoidance procedures in diagnosed AD are insufficient. Regardless, some guidelines acknowledge the benefit of mattress and pillow covers in patients with dust mite sensitization that are unresponsive to optimal AD management. Most clinical trials investigating allergen-specific immunotherapy (AIT) as a potential treatment for AD were done with adult patients; a scarce number of studies looked into the efficacy of AIT as a treatment option in children suffering from AD, with conflicting data among them. One of the most feasible of these studies showed significant improvement of AD outcomes only in the mild/moderate group, but not in the severe group. Uncontrolled studies are hard to interpret, considering the natural history of remitting and relapsing of AD, in many of the patients, without clinical interventions. More AIT studies, especially pediatric studies, are required in order to either prove the reproducibility of positive results or to deny its effectiveness.

A rapid desensitization protocol in a case of drotaverine-induced serum sickness-like reaction in a pregnant woman: A case report.

Drotaverine is an antispasmodic drug used to treat gastrointestinal and genitourinary smooth muscle spasms. There are very few hypersensitivity reactions reported. Serum sickness-like disease is an immune-complex-mediated hypersensitivity reaction that presents with some typical features that include rash, fever and articular impairment sometimes associated with liver and renal dysfunctions, beginning 1-2 weeks after exposure to a culprit drug. Diagnosis is a clinical one, made usually on the basis of knowledge obtained by medical history and physical examination. Desensitization usually is recommended for type I reaction, but may be a solution for this type of immunological reaction when other therapeutic alternatives are ineffective or do not exist. We report the case of a 29-year-old pregnant female who developed serum sickness-like reaction after 5 days of daily drotaverine oral administration. The patient required antispasmodic treatment, with this drug, having a pregnancy with an imminent risk of abortion and the other therapeutic alternatives being ineffective. She underwent a rapid 7-step oral drotaverine desensitization protocol without recurrence of serum sickness-like reaction. To our knowledge, this is the first case report of desensitization to drotaverine, previously involved in a serum sickness-like reaction.