ABSTRACT
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.
Subject(s)
Exanthema , Hypersensitivity, Delayed , Multiple Myeloma , Humans , Lenalidomide/therapeutic use , Multiple Myeloma/drug therapy , Retrospective Studies , Exanthema/chemically induced , Exanthema/therapy , Hypersensitivity, Delayed/chemically induced , Hypersensitivity, Delayed/therapyABSTRACT
SARS CoV-2 virus has infected more than 200 million people worldwide and more than 4.4 million in Indonesia. The vaccination program has become one of the solutions launched by many countries globally, including Indonesia, to reduce the transmission rate of COVID-19. Various vaccination platforms are produced, such as inactivated, viral vector, mRNA, and protein subunit. The vaccination booster program with mRNA platform (Moderna) was launched by the Indonesian government to give better protection for health care workers, particularly from delta variant. In this case report, we discuss one of the typical side effects of Moderna vaccine, which is referred to as the COVID arm.
Subject(s)
Acetaminophen/administration & dosage , COVID-19 Vaccines , COVID-19/prevention & control , Drug-Related Side Effects and Adverse Reactions , Hypersensitivity, Delayed , Skin/pathology , 2019-nCoV Vaccine mRNA-1273 , Analgesics, Non-Narcotic/administration & dosage , Biopsy/methods , COVID-19/epidemiology , COVID-19 Vaccines/administration & dosage , COVID-19 Vaccines/adverse effects , Drug-Related Side Effects and Adverse Reactions/etiology , Drug-Related Side Effects and Adverse Reactions/physiopathology , Drug-Related Side Effects and Adverse Reactions/therapy , Female , Fever/drug therapy , Fever/etiology , Humans , Hypersensitivity, Delayed/chemically induced , Hypersensitivity, Delayed/physiopathology , Hypersensitivity, Delayed/therapy , Injection Site Reaction/diagnosis , Injection Site Reaction/etiology , Injection Site Reaction/physiopathology , Middle Aged , Physicians , SARS-CoV-2 , Treatment Outcome , Vaccination/methodsABSTRACT
Metal hypersensitivity (MHS) and trunnionosis are being looked at more frequently. Both entities pose a difficult concern for surgeons and patients alike. This commentary highlights the similarities and differences between the 2 conditions. When a surgeon suspects either MHS or trunnionosis, both should be considered in the differential diagnosis. Both conditions are rare and should be considered a diagnosis of exclusion. The commentary proposes an outline on how to diagnose and treat the 2 entities.
Subject(s)
Arthroplasty, Replacement, Hip/adverse effects , Hip Prosthesis/adverse effects , Hypersensitivity, Delayed/diagnosis , Hypersensitivity, Delayed/etiology , Metals/adverse effects , Prosthesis Failure/adverse effects , Diagnosis, Differential , Humans , Hypersensitivity, Delayed/therapyABSTRACT
Despite the strong evidence for the immunomodulatory activity of mesenchymal stromal cells (MSCs), clinical trials have so far failed to clearly show benefit, likely reflecting methodological shortcomings and lack of standardization. MSC-mediated tissue repair is commonly believed to occur in a paracrine manner, and it has been stated that extracellular vesicles (EVs) secreted by MSCs (EVMSC) are able to recapitulate the immunosuppressive properties of parental cells. As a next step, clinical trials to corroborate preclinical studies should be performed. However, effective dose in large mammals, including humans, is quite high and EVs industrial production is hindered by the proliferative senescence that affects MSCs during massive cell expansion. We generated a genetically modified MSC cell line overexpressing hypoxia-inducible factor 1-alpha and telomerase to increase the therapeutic potency of EVMSC and facilitate their large-scale production. We also developed a cytokine-based preconditioning culture medium to prime the immunomodulatory response of secreted EVs (EVMSC-T-HIFc). We tested the efficacy of this system in vitro and in a delayed-type hypersensitivity mouse model. MSC-T with an HIF-1α-GFP lentiviral vector (MSC-T-HIF) can be effectively expanded to obtain large amounts of EVs without major changes in cell phenotype and EVs composition. EVMSC-T-HIFc suppressed the proliferation of activated T-cells more effectively than did EVs from unmodified MSC in vitro, and significantly blunted the ear-swelling response in vivo by inhibiting cell infiltration and improving tissue integrity. We have developed a long-lived EV source that secretes high quantities of immunosuppressive EVs, facilitating a more standard and cost-effective therapeutic product.
Subject(s)
Extracellular Vesicles/transplantation , Hypersensitivity, Delayed/therapy , Hypoxia-Inducible Factor 1, alpha Subunit/genetics , Immunomodulation , Mesenchymal Stem Cell Transplantation/methods , Mesenchymal Stem Cells/metabolism , T-Lymphocytes/immunology , Animals , Cell Line , Cell Proliferation , Cells, Cultured , Cytokines/pharmacology , Dental Pulp/cytology , Extracellular Vesicles/immunology , Genetic Vectors/genetics , Green Fluorescent Proteins/genetics , Green Fluorescent Proteins/metabolism , Humans , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , Lentivirus/genetics , Male , Mesenchymal Stem Cells/drug effects , Mice , Mice, Inbred BALB C , Protein Engineering/methods , Recombinant Proteins/genetics , Recombinant Proteins/metabolism , T-Lymphocytes/physiology , Telomerase/genetics , Telomerase/metabolism , Young AdultSubject(s)
Allergens/immunology , Desensitization, Immunologic/methods , Drug Hypersensitivity/therapy , Hypersensitivity, Delayed/therapy , Lenalidomide/immunology , T-Lymphocytes/immunology , Aged , Drug Hypersensitivity/diagnosis , Humans , Hypersensitivity, Delayed/diagnosis , Immunologic Tests , Lymphocyte Activation , Male , Treatment OutcomeABSTRACT
: Wine, beer, liquor, and spirits are widely consumed in many cultures across the globe, and for some individuals, ingestion, cutaneous contact, or other exposure can lead to dermatologic findings. However, there currently exist no comprehensive reviews on alcohol-related dermatitis. Herein, we will provide an overview of alcohol-related dermatitis and contact urticaria, including the epidemiology and clinical manifestations, potential allergens found in alcoholic beverages, testing approaches, and strategies for allergen avoidance.
Subject(s)
Alcoholic Beverages/adverse effects , Dermatitis, Allergic Contact/epidemiology , Urticaria/epidemiology , Balsams/adverse effects , Beer/adverse effects , Chromium/adverse effects , Citrus/adverse effects , Cobalt/adverse effects , Dermatitis/epidemiology , Dermatitis/physiopathology , Dermatitis/therapy , Dermatitis, Allergic Contact/etiology , Dermatitis, Allergic Contact/physiopathology , Dermatitis, Allergic Contact/therapy , Food Preservatives/adverse effects , Gold/adverse effects , Humans , Hypersensitivity, Delayed/epidemiology , Hypersensitivity, Delayed/etiology , Hypersensitivity, Delayed/physiopathology , Hypersensitivity, Delayed/therapy , Hypersensitivity, Immediate/epidemiology , Hypersensitivity, Immediate/etiology , Hypersensitivity, Immediate/physiopathology , Hypersensitivity, Immediate/therapy , Isothiocyanates/adverse effects , Nickel/adverse effects , Propylene Glycol/adverse effects , Sulfites/adverse effects , Urticaria/etiology , Urticaria/physiopathology , Urticaria/therapy , Wine/adverse effectsABSTRACT
Because of their inert character and desired biocompatibility, titanium implants have been universally accepted as safer alternatives to the conventional stainless steel orthopedic implants; however, recent emergence of type IV hypersensitivity reactions to titanium have included eczema, contact dermatitis, a prolonged febrile state, sterile osteonecrosis, and impaired fracture and wound healing. This report presents a patient with postoperative incision dehiscence and devascularization of surfaces in contact with titanium hardware after undergoing a double calcaneal osteotomy and a first metatarsal-cuneiform arthrodesis using titanium alloy implants. Titanium hypersensitivity was confirmed in this case through standard allergy patch testing by a board-certified immunologist. Complete healing occurred after diagnosis of the titanium allergy and hardware explant. To our knowledge, this is one of a few known allergies to titanium implants after foot and ankle surgery.
Subject(s)
Arthrodesis/adverse effects , Arthrodesis/instrumentation , Hypersensitivity, Delayed/etiology , Metatarsal Bones/surgery , Titanium/adverse effects , Adult , Female , Flatfoot/surgery , Humans , Hypersensitivity, Delayed/diagnosis , Hypersensitivity, Delayed/therapy , Osteotomy/adverse effects , Tarsal Bones/surgeryABSTRACT
Lenalidomide is an immunomodulatory agent that belongs to a family of IMiDs used to treat multiple myeloma. Hypersensitivity and skin reactions are adverse effects of lenalidomide that may lead to discontinuation of its use for multiple myeloma making them contraindicated to other IMiD therapies. Desensitization protocols have been developed to desensitize patients to lenalidomide skin reaction and rash. We report a case series of 5 patients undergoing slow lenalidomide desensitization protocol in an outpatient cancer center setting. Four of the five patients were able to be successfully desensitized to lenalidomide. We also demonstrate safety of using slow lenalidomide desensitization while on combination therapy for control of multiple myeloma.
Subject(s)
Desensitization, Immunologic/methods , Drug Eruptions/therapy , Exanthema/therapy , Hypersensitivity, Delayed/therapy , Immunologic Factors/administration & dosage , Lenalidomide/administration & dosage , Multiple Myeloma/drug therapy , Aged , Aged, 80 and over , Cancer Care Facilities , Dose-Response Relationship, Drug , Drug Administration Schedule , Drug Eruptions/etiology , Exanthema/chemically induced , Exanthema/immunology , Female , Humans , Hypersensitivity, Delayed/chemically induced , Hypersensitivity, Delayed/immunology , Immunologic Factors/adverse effects , Immunologic Factors/immunology , Lenalidomide/adverse effects , Lenalidomide/immunology , Male , Middle Aged , Multiple Myeloma/immunology , Outpatient Clinics, Hospital , Skin/drug effects , Skin/immunology , Time Factors , Treatment OutcomeABSTRACT
Many notable advances in drug allergy, urticaria, angioedema, and anaphylaxis were reported in 2018. Broad-spectrum antibiotic use and, consequently, antibiotic resistance are widespread, and algorithms to clarify ß-lactam allergy and optimize antibiotic use were described. Meaningful data emerged on the pathogenesis of delayed drug hypersensitivity reactions. Progress not only in defining biomarkers but also in understanding the effect on quality of life and developing better treatments has been made for patients with chronic idiopathic urticaria. Patients with hereditary angioedema (HAE) have gained additional access to highly efficacious therapies, with associated improvements in quality of life, and some progress was made in our understanding of recurrent angioedema in patients with normal laboratory results. Guidelines have defined clear goals to help providers optimize therapies in patients with HAE. The epidemiology and triggers of anaphylaxis and the mechanisms underlying anaphylaxis were elucidated further. In summary, these disorders (and labels) cause substantial burdens for individual persons and even society. Fortunately, publications in 2018 have informed on advancements in diagnosis and management and have provided better understanding of mechanisms that potentially could yield new therapies. This progress should lead to better health outcomes and paths forward in patients with drug allergy, urticaria, HAE, and anaphylaxis.
Subject(s)
Anaphylaxis , Angioedema , Drug Hypersensitivity , Quality of Life , Urticaria , beta-Lactams/adverse effects , Anaphylaxis/chemically induced , Anaphylaxis/immunology , Anaphylaxis/therapy , Angioedema/chemically induced , Angioedema/immunology , Angioedema/pathology , Angioedema/therapy , Drug Hypersensitivity/immunology , Drug Hypersensitivity/pathology , Drug Hypersensitivity/therapy , Humans , Hypersensitivity, Delayed/chemically induced , Hypersensitivity, Delayed/immunology , Hypersensitivity, Delayed/pathology , Hypersensitivity, Delayed/therapy , Urticaria/chemically induced , Urticaria/immunology , Urticaria/pathology , Urticaria/therapy , beta-Lactams/therapeutic useSubject(s)
Desensitization, Immunologic , Drug Hypersensitivity/etiology , Drug Hypersensitivity/therapy , Hypersensitivity, Delayed/etiology , Hypersensitivity, Delayed/therapy , Immunologic Factors/adverse effects , POEMS Syndrome/complications , Thalidomide/analogs & derivatives , Aged , Biomarkers , Drug Hypersensitivity/diagnosis , Female , Humans , Hypersensitivity, Delayed/diagnosis , Immunologic Factors/therapeutic use , Magnetic Resonance Imaging , POEMS Syndrome/diagnosis , POEMS Syndrome/drug therapy , Thalidomide/adverse effects , Thalidomide/therapeutic use , Treatment OutcomeSubject(s)
Antitubercular Agents/adverse effects , Drug Eruptions/etiology , Drug Hypersensitivity/etiology , Exanthema/chemically induced , Hypersensitivity, Delayed/chemically induced , Algorithms , Antitubercular Agents/therapeutic use , Drug Eruptions/diagnosis , Drug Eruptions/therapy , Drug Hypersensitivity/diagnosis , Drug Hypersensitivity/therapy , Exanthema/diagnosis , Exanthema/therapy , Humans , Hypersensitivity, Delayed/diagnosis , Hypersensitivity, Delayed/therapy , Practice Guidelines as TopicSubject(s)
Antineoplastic Agents, Alkylating/adverse effects , Bendamustine Hydrochloride/adverse effects , Desensitization, Immunologic , Drug Hypersensitivity/therapy , Hypersensitivity, Delayed/therapy , Adult , Drug Hypersensitivity/diagnosis , Humans , Hypersensitivity, Delayed/diagnosis , Male , Skin TestsSubject(s)
Bortezomib/adverse effects , Desensitization, Immunologic , Drug Hypersensitivity/immunology , Drug Hypersensitivity/therapy , Hypersensitivity, Delayed/immunology , Hypersensitivity, Delayed/therapy , Aged , Aged, 80 and over , Desensitization, Immunologic/methods , Drug Hypersensitivity/metabolism , Female , Humans , Hypersensitivity, Delayed/metabolism , Immune Tolerance , Male , Oligopeptides/adverse effects , Skin/immunology , Skin/metabolism , Skin/pathology , T-Lymphocyte Subsets/immunology , T-Lymphocyte Subsets/metabolismABSTRACT
No Abstract.
Subject(s)
Desensitization, Immunologic , Diazoxide/adverse effects , Drug Hypersensitivity/immunology , Drug Hypersensitivity/therapy , Child, Preschool , Desensitization, Immunologic/methods , Diazoxide/therapeutic use , Drug Hypersensitivity/diagnosis , Female , Humans , Hypersensitivity, Delayed/diagnosis , Hypersensitivity, Delayed/immunology , Hypersensitivity, Delayed/therapy , Nesidioblastosis/complications , Nesidioblastosis/drug therapy , Treatment Failure , Treatment OutcomeABSTRACT
Successful desensitization to mild to moderate delayed cutaneous adverse reaction to antibiotics has been described in a limited number of antibiotics and found to be safe. However, there are ample opportunities to standardize protocols for delayed cutaneous adverse reactions to antibiotics.
Subject(s)
Allergens/immunology , Anti-Bacterial Agents/immunology , Drug Hypersensitivity/therapy , Hypersensitivity, Delayed/therapy , Skin/immunology , Desensitization, Immunologic , Drug Hypersensitivity/diagnosis , Humans , Hypersensitivity, Delayed/diagnosis , Skin TestsSubject(s)
Arthropod Venoms/therapeutic use , Hypersensitivity, Delayed/diagnosis , Insect Bites and Stings/diagnosis , Urticaria/diagnosis , Wasps/immunology , Animals , Female , Humans , Hypersensitivity, Delayed/immunology , Hypersensitivity, Delayed/physiopathology , Hypersensitivity, Delayed/therapy , Immunoglobulin E/biosynthesis , Immunotherapy/methods , Insect Bites and Stings/immunology , Insect Bites and Stings/physiopathology , Insect Bites and Stings/therapy , Middle Aged , Urticaria/immunology , Urticaria/physiopathology , Urticaria/therapy , Wasps/chemistry , Wasps/pathogenicityABSTRACT
Most immune-mediated adverse drug reactions (IM-ADRs) involve the skin, and many have additional systemic features. Severe cutaneous adverse drug reactions (SCARs) are an uncommon, potentially life-threatening, and challenging subgroup of IM-ADRs with diverse clinical phenotypes, mechanisms, and offending drugs. T-cell-mediated immunopathology is central to these severe delayed reactions, but effector cells and cytokines differ by clinical phenotype. Strong HLA-gene associations have been elucidated for specific drug-SCAR IM-ADRs such as Stevens-Johnson syndrome/toxic epidermal necrolysis, although the mechanisms by which carriage of a specific HLA allele is necessary but not sufficient for the development of many IM-ADRs is still being defined. SCAR management is complicated by substantial short- and long-term morbidity/mortality and the potential need to treat ongoing comorbid disease with related medications. Multidisciplinary specialist teams at experienced units should care for patients. In the setting of SCAR, patient outcomes as well as preventive, diagnostic, treatment, and management approaches are often not generalizable, but rather context specific, driven by population HLA-genetics, the pharmacology and genetic risk factors of the implicated drug, severity of underlying comorbid disease necessitating ongoing treatments, and cost considerations. In this review, we update the basic and clinical science of SCAR diagnosis and management.
Subject(s)
Drug Hypersensitivity/diagnosis , HLA Antigens/genetics , Hypersensitivity, Delayed/diagnosis , Skin/immunology , T-Lymphocytes/immunology , Alleles , Animals , Drug Hypersensitivity/therapy , Genetic Predisposition to Disease , Humans , Hypersensitivity, Delayed/therapy , Immunoglobulin E/blood , Risk , Stevens-Johnson SyndromeABSTRACT
Antibiotics are the most common class of medications that individuals report allergy or intolerance to. Adverse reactions are reported at a predictable rate with all antibiotic use that vary by antibiotic. Antibiotic allergy incidence rates are sex dependent, higher in females than in males. Most of these events are not reproducible or immunologically mediated. Antibiotic allergy prevalence increases with increasing age and is more common in hospitalized populations and in populations that use more antibiotics. Determining potential mechanisms for the observed symptoms of the adverse reactions is the starting point for effective management of antibiotic hypersensitivity. Skin testing and direct challenges are the primary tools used to determine acute tolerance in 2017. Commercially available in vitro testing is not currently clinically useful in determining antibiotic hypersensitivity, with rare exceptions. Desensitization can be used when acute-onset immunologically mediated hypersensitivity is confirmed to safely administer a needed antibiotic. Desensitization is not possible when clinically significant T-cell-mediated delayed-type hypersensitivity is present. Effective management of antibiotic allergy is an important part of a comprehensive antibiotic stewardship program.
Subject(s)
Anti-Bacterial Agents/adverse effects , Desensitization, Immunologic/methods , Drug Hypersensitivity/diagnosis , Hypersensitivity, Delayed/diagnosis , T-Lymphocytes/immunology , Age Factors , Allergens/therapeutic use , Animals , Anti-Bacterial Agents/therapeutic use , Drug Hypersensitivity/therapy , Female , Humans , Hypersensitivity, Delayed/therapy , Male , Prevalence , Sex Factors , Skin TestsABSTRACT
Tranexamic acid is an anti-fibrinolytic agent frequently used in pediatric surgery. Common side effects include nausea, flushing, and headache, but in rare instances, it may produce anaphylaxis; with only one previously reported case in a 72-year-old man. We report a case of a delayed anaphylactic reaction in a pediatric patient undergoing posterior spine fusion; and discuss the intraoperative management of the acute event, immunologic confirmation, and subsequent anesthetic approach.