Academic literature on the topic 'Type IV hypersensitivity reactions'

Antibiotics are commonly prescribed to treat a variety of bacterial infections. As with all medications, hypersensitivity reactions may occur and clinicians should be able to recognize them accurately and recommend appropriate management. Antibiotic related hypersensitivity reactions may be one of four different types: Type I reactions, which are IgE mediated and may lead to anaphylaxis; Type II reactions that are antibody-mediated and may result in thrombocytopenia, neutropenia, or hemolytic anemia; Type III reaction that involves an immune complex formation such as vasculitis; and Type IV reactions that consist of four subtypes and typically include a rash of varying level of severity with or without systemic signs and symptoms. Herein, we describe the mechanisms of different types of allergic reactions to commonly prescribed antibiotics and offer recommendations for management. Further, we briefly refer to antibiotic reactions that mimic hypersensitivity reactions but are not immune mediated, such as pseudoallergies and serum sickness-like reactions.

Glaucoma is the leading cause of irreversible blindness in the world. Currently, glaucoma affects more than 60 million people and it is expected to reach 76 million by 2020 (1). Introduction Glaucoma is the leading cause of irreversible blindness in the world. Currently, glaucoma affects more than 60 million people and it is expected to reach 76 million by 2020.1 There are two kinds of chronic glaucoma: Open-angle glaucoma Closed-angle glaucoma 2 Glaucoma is characterized as an optic neuropathy determined by structural changes and functional deficiencies. Primary glaucoma (open-angle) is the most prevalent in the general population (40-80 years 3-4%), and it constitutes the leading cause of irreversible vision loss in industrialized countries.3 Current pharmacological treatments seek to obtain optimal local tolerance, using preservative-free formulations in simple presentations or combinations, both in single-dose and multi-dose. Contact dermatitis is caused by an ample inflammation which arises from the release of pro-inflammatory cytokines from keratinocytes, usually in response to chemical stimuli. Mainly, this causes alteration of the skin barrier, cellular changes at the epidermal level, and release of cytokines.4 Allergic contact dermatitis caused by eye medication is mainly attributed to active ingredients. But other excipient ingredients should also be analyzed in addition to the products on an "as is" basis.5 There is an entity called the Ocular Pharmacological Intolerance Syndrome (SIFO, in Spanish), which is an intolerance to the drop-based treatment for glaucoma which causes: conjunctival hyperemia, itching, sensation of foreign body presence, light sensitivity, lacrimation, and blepharitis. Exceptionally, these symptoms could also be present: superficial keratitis, deposits on the cornea, palpebral swelling, and blurred vision. SIFO in some of its degrees can also be caused by other topical drugs such as dyes, anesthetics, antibiotics, anti-inflammatories, antivirals, etc. This paper presents a case of allergic contact dermatitis in a patient sensitized to timolol present in the ophthalmic preparations the patient used as a treatment for glaucoma. Clinical Case The patient is a 37-year-old male who was diagnosed 2 years ago with bilateral primary open angle glaucoma (POAG), with prescription of dorzolamide and a topical ß-adrenergic blocker (timolol) in drops, twice a day. In August of 2019, the patient seeked medical help for conjunctival hyperemia, itching, and inflammation of the eyelids of both eyes followed by erythematous dermatitis, which improved once the treatment was suspended. These symptoms repeated when the drug was used. The patient was known to be hypertensive and received treatment with enalapril 10 mg and Aspirin 125 mg. The patient was not known to be asthmatic or allergic to drugs, nor was he known to be diabetic. Thinking of a hypersensitivity reaction, a provocation test with timolol was performed and there was no immediate reaction. Then, provocation tests were performed, first with enalapril and later with aspirin. Both were negative for an immediate hypersensitivity reaction. Given the clinical situation of the patient and the risk of being without treatment, the patient was suggested to consult his ophthalmologist to look for another alternative treatment. While waiting for a response, the patient received the patch test with all the prescribed active ingredients of the drug used, through drops; The results were negative in the reading at 48 hours. At 96 hours the patient was called, who for work reasons could not attend the clinic, clarifying however that there had been no changes. After 7 days he was screened at the clinic, and no changes were found. In some cases where different beta-blockers for ophthalmic use are tested, and which have caused dermatitis in the eyelid area, negative results can be observed in the patch test. This occurs because the skin of the eyelids has greater penetrability than the skin of the back, where skin patches are usually applied.6,7 This would explain why the epicutaneous tests were negative for this patient, and the conjunctival provocation tests were positive. Subsequently, provocation tests were performed using the provocation technique with increasing dilutions of 1/1000, 1/100, 1/10 and concentrated. As first dose tears were used as placebo, checking every 15 minutes the pulse of the patient as well as the pressure, the presence of pruritus, irritation, erythema, chemosis and epiphora. The patient remained in the hospital from 2 pm to 8 pm and the provocation was negative. The patient returned after 24 hours, and the provocation was once again negative. At 48 hours the reactions were positive (timolol maleate 0, 5%), with irritation, tearing, chemosis, and erythema in both eyelids. Discussion There are numerous substances contained in ophthalmic preparations responsible for producing true allergic contact reactions. The most important group responsible for this frequency is constituted by antimicrobial agents, and preservatives such as thimerosal, benzyl alcohol, benzalkonium chloride (BAC), ethylenediamine and parabens, among others.8,9 In recent years, there have been reports of contact dermatitis due to beta-blockers used in the treatment of glaucoma such as timolol 10, levobunolol 11, carteolol 12 or betaxolol 13. In all cases, eczematous-like reactions on the eyelids, blepharoconjunctivitis, itching with inflammation and edema, conjunctival chemosis, and blurred vision manifested with different intensity. Timolol is a non-selective beta-blocker commonly more preferred than other agents in terms of efficacy, adverse effects, and cost. Its topical application can produce a foreign body sensation, pruritus, conjunctivitis and in some instances contact dermatitis.14 Several authors have suggested the possible existence of cross reactions between the different beta-blockers 15,16, so that the replacement of the drug involved in sensitization by another one from the same family would not proceed. Although there are many medications and ophthalmic products which can cause adverse effects at the ocular level, fortunately in most cases these adverse effects reverse once the medication is discontinued. However, when these adverse effects are not detected early, some reactions can prolong causing irreversible eye damage.17 Bibliography Patch test with timolol alone, timolol dorzolamide and excipients, enalapril and ASA Negative patch test at 72 hours Positive conjunctival provocative test at 48 hours

The purpose of the study is to analyze the reaction and types of hypersensitivity. The study discusses the reaction of hypersensitivity occurs in individuals who have previously been exposed to an antigen that has created an immune response to it (sensitization). there are 4 groups of hypersensitivity reactions, namely Type I (anaphylactic reaction), type II (cytotoxic reaction), type III (immune complex reaction), type IV (slow type reaction). Hypersensitivity reactions can occur in two situations. first, the response to foreign antigens (microbes and non-infectious environmental antigens) which can cause tissue damage, especially if the reaction is repeated and uncontrolled. Second, the immune response can act directly against self-antigens (autologs) as a result of failure to tolerate self (self-tolerance).

SummaryLocalized hypersensitivity reactions to subcutaneous heparin injections have been described since 1952. Yet, the incidence of these reactions, which are distinct from skin lesions associated with heparin-induced thrombocytopenia type II (HIT II), remains uncertain. However, in the last 10 years an increasing number of patients have been reported, leading to the assumption that cutaneous hypersensitivity reactions towards heparin are underreported. Clinically patients present with itching, sometimes infiltrated, and blistering erythemas at the injection sites of heparins. The diagnosis of cutaneous heparin allergy may, on the one hand, lead to delay of required medical or surgical treatment. On the other hand, delayed initiation of treatment may lead to a generalized eczematous reaction. Hence, from review of 223 cases of patients with cutaneous hypersensitivity reactions to heparin, we here summarize the clinical picture of cutaneous type IV allergic reactions, define risk factors on both the patient- and drug-side, and give an overview of principle therapeutic alternatives, as well as recommendations for treatment options for emergency and elective patients. As the proposed management of patients with cutaneous hypersensitivity reactions to heparin may have fatal consequences when applied in patients with HIT type II, diagnosis of skin lesions in heparin-treated patients needs to be precise.

The recently extended use of mRNA vaccines due to the COVID-19 pandemic has allowed the description of multiple cutaneous adverse events including local injection site reactions, urticaria, and morbilliform eruptions. COVID-19 vaccine-related cutaneous reaction patterns can be divided into type Ⅰ hypersensitivity reactions, type Ⅳ hypersensitivity reactions, autoimmune-related, and functional angiopathies based on pathogenesis. Erythema multiforme (EM), a type IV hypersensitivity reaction, has also been reported from several centers. We experienced the remarkable improvement of COVID-19 vaccine-related EM with systemic administration of prednisolone and summarized six cases experienced in our department.

Lidocaine is a commonly used local anesthetic in the field of dentistry. It has been known to cause allergic reactions, mainly immunoglobulin (IgE)-mediated and T-cell –mediated type IV reactions, which require the use of alternative drugs without adverse effects. Here we present the case of a 29 year old female patient who developed Type IV hypersensitivity reaction in the vicinity of the injection site after the administration of lidocaine local anesthetic for performing exodontia. Levocetrizine tablet was prescribed in order to relieve the symptoms of the reaction. Levocetrizine is a selective, potent, oral histamine H(1) receptor antagonist that is used for the symptomatic treatment of allergic rhinitis and chronic idiopathic urticaria. It has been reported to be effective and generally well tolerated by the patients. In our case also it was able to cure Type IV hypersensitivity reaction to lidocaine without producing any adverse events. Apart from curing allergic rhinitis and urticaria, levocetrizine is a wonderful option for treating Type IV hypersensitivity reaction to a local anesthetic, and it hardly produces any adverse effect. More cases are required to be reported in the future in order to support this article.

Delayed hypersensitivity reactions are inflammatory reactions initiated by mononuclear leukocytes. These reactions are mediated by T cells and monocytes/macrophages rather than by antibodies. We describe a case of 50 years old man with lung type IV hypersensitivity. The case of lung delayed hypersensitivity presented has some particular histopathological and immunohistochemical features. The diagnosis of lung delayed type hypersensitivity requires analysis of correlation between clinic, radiographic, physiologic and pathologic criteria.

T cells enter tissues and are activated by antigen-presenting cells to produce cytokines that cause inflammation in the local area. In allergic contact dermatitis, drug eruptions, asthma, and autoimmune disorders, CD8+ T lymphocytes mediate DTH reactions. As an example of this type IV hypersensitivity, chronic DTH reactions, contact hypersensitivity, and hypersensitivity pneumonitis are all examples. Infiltration of an antigen-exposed region by Th1 cells and macrophages, which inflict tissue damage, is the primary cause of the delayed onset of symptoms. It has thus been outlined that this delayed hypersensitivity reaction.

The investigations have given rise to the following findings: 1. CsA is an effective immunosuppressant of both the induction and elicitation phases of tuberculin-like and contact delayed-type hypersensitivity (DTH) and of the induction phase of Jones-Mote hypersensitivity. 2. The effective suppression of tuberculin-like DTH responses in the guinea pig is not dependent upon cyclophosphamide-sensitive suppressor cells. 3. Topically applied CsA inhibits the elicitation of contact dermatitis in experimental animals. 4. The kinetics of percutaneous CsA absorption have been determined, as has the extent to which this mode of drug delivery obviates systemic toxicity. 5. The investigation of CsA-induced DTH enhancement indicates that the phenomenon is restricted to cellular as opposed to humoral responses, develops some days after drug withdrawal and can be reversed by the administration of putative suppressor cells from immunised but untreated animals. 6. CsA is able to effectively inhibit T cell dependent hyper-eosinophilia. It would appear that the effects of CsA on DTH responses and on T dependent eosinophilia occur primarily by the inhibition of T helper cell function. Enhancement phenomena seem to arise from drug impaired development of antigen-specific suppressor cells which, following drug withdrawal, fail to develop, in contrast to the maturation of T effector cells. Although the phenomenon of enhancement may limit the potential of CsA in the control of diseases in which DTH responses are a component, topical application is effective and may well be suitable for use over a prolonged period without systemic toxicity.

Adverse drug reactions remain a major health issue with delayed type hypersensitivity reactions developing in a high number of individuals. The cellular immunological processes that underlie drug-specific responses in hypersensitive patients have been previously described; however the involvement of the humoral immune system has not been studied in great detail. Consequently, this thesis explores the nature of the piperacillin-specific B cell response in hypersensitive patients and compares the cellular and humoral immune response that develops in patients with cystic fibrosis (CF) exposed to repeated courses of the drug. Initial studies involved characterization of B cell proliferation, B cell phenotype and the nature of total and drug-specific IgG antibody secretions using peripheral blood mononuclear cells (PBMC) from hypersensitive patients. For comparison PBMCs from 2 groups of individuals were assessed: piperacillin naïve healthy volunteers and piperacillin tolerant patients with CF. ELISA, and ELISpot were used to detect piperacillin-specific B cells responses and IgG secretion. T lymphocyte proliferation was assessed with the lymphocyte transformation test (LTT). T lymphocytes from hypersensitive patients, but not tolerant patients or naïve donors were stimulated to proliferate in the presence of the drug. The peak concentration for T cell activation was 1 mM. Phenotypic assessment of hypersensitive patients B-cells revealed an increase in CD19+CD27+ expression in response to piperacillin treatment in vitro. IgG secreting immortalized B-cell lines also expressed a pure CD19+CD27+ phenotype. Piperacillin stimulation of hypersensitive patient PBMC also led to an increase in the secretion of IgG. In contrast, IgG secretion was not detectable following piperacillin stimulation of PBMC from tolerant patients and healthy controls. Western blotting and mass spectrometric methods were applied to characterize -lactam-protein covalent binding. Bovine serum albumin (BSA) binding was time- and concentration-dependent with hapten densities (i.e., the extent of selective lysine residue modification) and anti-piperacillin antibody binding affinity increasing with increasing molar ratios. Lysine residues in BSA at positions 4, 12, 131, 132, 136, 211, 431, 524, and 537 were modified by piperacillin. Epitope profiles also showed similar lysine residues were modified with amoxicillin, benzylpenicillin and flucloxacillin though the extent of ionisation at each site of modification was drug-dependent. A hapten inhibition ELISA used to assess the specificity of the antidrug antibodies revealed the total antibody binding to aztreonam, amoxycillin, benzylpenicillin and penicillin V BSA adducts. This indicates a lack of cross-reactivity with piperacillin-specific IgG antibodies. Subsequently, LTT and ELISA were employed to screen the piperacillin-specific T cell response and IgG antibodies during piperacillin therapy. It was established that piperacillin-specific T cells were detectable on and following clinical diagnosis of hypersensitivity. Moreover, piperacillin-specific T cell responses were detected in a small number of patients currently classified as drug tolerant. A significant difference in piperacillin-specific IgG was observed when plasma form LTT positive and negative blood samples were compared. LTT positivity was associated with higher levels of piperacillin-specific IgG. Furthermore, a significant decrease in piperacillin-specific IgG was seen 24 h post-desensitisation (graded drug challenge). Piperacillin-specific T cell clones isolated from hypersensitive patients were used to explore the effect of plasma bearing anti-piperacillin IgG on the T cell response. Eleven piperacillin-specific CD4+ and CD8+ T-cell clones were generated from 2 hypersensitive patients. All clones were stimulated to proliferate with piperacillin in a concentration-dependent manner. IFN-γ and IL-5 secretion was seen to predominate following piperacillin stimulation. There were no differences in piperacillin-specific T-cell proliferation when piperacillin-specific antibody bearing plasma and plasma from naive volunteers were compared. However, attenuation in IFN-γ secretion was observed with plasma bearing anti-piperacillin antibodies alone. Collectively, the data presented in this thesis begins to describe the different components of the drug-specific humoral and cellular immune response that develops in piperacillin hypersensitive patients with CF.

Introdução: O saco endolinfático tem sido apontado como o alvo das reações imuno-alérgicas da orelha interna. A prevalência de alergia em pacientes com Doença de Ménière foi estabelecida em torno de 41,6% para inalantes e 26,6% para alimentos, por Derebery em 2000, dados aumentados em relação à prevalência de alergia na população em geral, que, no Brasil, varia de 9% a 30% para inalantes e de 1% a 3% para alimentos. Objetivos: Avaliar a prevalência de reações de hipersensibilidade tipo I a inalantes e alimentos na população do setor de Otoneurologia do Hospital das Clínicas da Faculdade de Medicina de São Paulo e descrever os sintomas vestibulares dos pacientes. Casuística e método: Setenta e cinco pacientes com distúrbios do equilíbrio de origem periférica foram submetidos a questionário de caracterização clínica de sintomas cócleo-vestibulares e teste cutâneo (prick test) para 13 inalantes e 5 alimentos. Resultados: Vinte e cinco (33,3%) pacientes apresentaram prick test positivo a pelo menos um alérgeno inalante e 6 (8%) a pelo menos um alérgeno alimentar. Quatro pacientes apresentaram prick test positivo na ausência de sintomas alérgicos. Prevaleceu a queixa de tontura de caráter rotatório em proporções semelhantes entre os pacientes com prick test positivo e negativo. Conclusão: A prevalência de reações de hipersensibilidade tipo I a inalantes e a alimentos na população avaliada foi maior do que na população em geral. Os sintomas vestibulares não diferiram entre os pacientes da amostra, com prick test positivo ou negativo. No entanto, deve-se obter maior número de amostra para que os dados sejam confiáveis.
Introduction: The endolymphatic sac has been pointed out as the target of immuno-allergic reactions in the inner ear. The prevalence of allergy in patients with Ménières disease was established as approximately 41,6% for inhalants and 26,6% for food by Derebery in 2000, an increase in the data in relation to that of the prevalence of allergy in the general population, which in Brazil varies from 9% to 30% for inhalants and from 1% to 3% for food. Objectives: To evaluate the prevalence of reactions to type I hypersensitivity to inhalants and food in the population of the Otoneurological Section of the Clinics Hospital of the University of São Paulo Medicine School and to describe the vestibular symptoms of the patients. Method: Seventy-five patients with peripheral equilibrium disturbances who had answered a questionnaire of clinical characterization regarding cochlear-vestibular symptoms and undergone prick test for 13 inhalants and 5 types of food. Results: Twenty-five (33,3%) of the patients were positive for the prick test and for at least one allergen inhalant and 6 (8%) for at least one food allergen. Four patients were positive for the prick test in the absence of allergy symptoms. There was a prevalence of the complaint of rotatory dizziness in similar proportions among the patients with positive and negative prick test. Conclusion: The presence of type I hypersensitivity reactions to inhalants and food in the population evaluated was greater than in the general population. The vestibular symptoms did not differ among the patients in the sample, neither with positive or negative prick test results. However, a sample of greater number should be obtained for a higher confidence level of data results.

Hypersensitivity reactions are aberrant immune responses that are provoked by innocuous extrinsic or self-antigens, are mediated by B-cells or T-cells, and may result in tissue or organ damage. Coombs and Gell classified hypersensitivity reactions into four types, based on the different immune responses: type I, or immediate hypersensitivity; type II, or antibody-mediated (humoral) cytotoxicity; type III, or immune-complex disease; and type IV, or delayed hypersensitivity. This chapter reviews the clinical features, diagnosis, and management of hypersensitivity reactions.