Hypersensitivity reactions (HR) are responses of the immune system that are part of a process in which the body fights off antigens. Both Coombs and Gell grouped hypersensitivity reactions into four forms together. Immediate hypersensitivity reactions (IHR) are known as type I, type II, and type III hypersensitivity reactions occur within 24 hours. Antibodies such as IgE, IgM, and IgG are involved in this immune reaction. 

Type I or Anaphylactic response 

IgE-mediated anaphylactic connectivity is a response to an environmental allergen like pollen, animal danders or dust mites, an agent that causes inflammation. Conditions that present themselves because of this ailment include allergic rhinitis, allergic conjunctivitis, and anaphylactic shock. Symptoms of anaphylaxis are caused by the release of high levels of histamine and leukotrienes. The release of high levels of these antibodies causes narrowing of the airways, which may become chronic. Allergic rhinitis causes production of watery nasal discharge outside and a sharp cough; allergic conjunctivitis gives rise to red eyes and is IgE-mediated. Allergy conjunctivitis comes along with rhinitis and is IgE mediated. In children, it is often that they suffer from food allergies and associated with malabsorption and celiac disease. Atopic dermatitis is an IgE-mediated skin disorder that has a similar immunopathogenesis to asthma and rhinitis. An autosomal recessive trait can produce a serious drug allergy, which results in an allergy with any hypersensitivity mechanism. 

Type II or Cytotoxic-Mediated Response 

Immunoglobulins (IgG and IgM) play a key role in the development of type II hypersensitivity reactions in ITP, AIHA, and AIHN by attacking the extracellular and cell surface proteins with the help of cytotoxic mechanisms. Also, Immune thrombocytopenia (ITP) is a condition in which the phagocytes are responsible for destroying the platelets, which are tagged by the antibodies in the bloodstream. There are two types of AIHA in IgG: IgG-mediated (warm AIHA) and IgM-mediated (cold AIHA), which manifests with the presence of jaundice as the main clinical sign. Infections with bacteria, viruses, and fungi, autoimmune diseases, lymphomas, and other autoimmune disorders can be the causes of autoimmune neutropenia. A fetal and neonatal hemolytic disease occurs when the placenta separates, and the child is exposed to anemia or jaundice when the IgG of the mother’s blood crosses the placental barrier. Myasthenia gravis remains a condition of extreme muscular fatigue and impairs eye muscle function to cause symptoms such as double vision, trouble swallowing, upper eyelid ptosis, and arm weakness. Goodpasture Syndrome describes a condition when antibodies fight against nephritis and lung bleeding. Blisters, showing up on the skin and mucous membranes, are a characteristic of pemphigus. It is a disease caused by antibodies to proteins of the desmosome such as desmoglein-1 and desmoglein-3. 

Type III or Immunocomplex reactions 

The Type III hypersensitivity reactions like serum sickness or Arthus reaction are antibody-mediated, in which IgM and IgG antibodies are extensively linked with soluble antigens as antigen-antibody complexes. This eventually unleashes the complement which releases neutrophil-attracting chemotactic agents, leading to local inflammation and tissue injury. Serum sickness, usually developed after mass injections of foreign antigens, bring about increased capillary leakage and the inflammatory processes similar to vasculitis and arthritis. It can also be triggered by the treatment with penicillin. Arthus reaction, a local reaction, manifests itself by the administration of small amounts of antigens that would be introduced for several times in the skin until detectable levels of the antibodies (IgG) are reached. The reaction itself is characterized by hyperemia and depending on the number of the foreign antigen doses, it can also be erythematous or hemorrhagic. 

Hypersensitivity reactions are common, affecting round 15% of the population worldwide. Allergic sicknesses in current years can be associated with factors like life-style changes, reduced breastfeeding, and air pollution. The hygiene speculation suggests that the IgE-mast mobile axis, that is concerned in type I allergic reaction reactions, has evolved as a response to fashionable hygienic conditions. 

Anaphylaxis, a intense and potentially existence-threatening hypersensitivity, influences 0.3% of the population, and approximately 1 in 3000 inpatients within the United States experience a immoderate allergy yearly. The prevalence of bronchitis is around 1.5% in Korea, and fungal infections, that may predispose humans to allergic bronchial allergies, may be as immoderate as 50% in internal towns. 

In Type I hypersensitivity reactions, IgE is produced. Mast cells and basophils have Fc receptors on them to which this type of immunoglobulin binds. The allergic response is initiated when these cells are activated by it. A reaction that involves histamine, lipid mediators, enzymes, and tumor necrosis factor (TNF) is caused by the release of mediators from mast cells during degranulation. This response results in tissue damage as well as inflammation. In Type II hypersensitivity reactions, the target is basement membranes. Myasthenia gravis, Lambert-Eaton syndrome and pemphigus are some examples of diseases caused by antibodies against these structures. Immune complex deposition (ICD) causes autoimmune diseases in Type III hypersensitivity reactions usually leading to inflammation due to excessive amounts of immune complexes remaining in circulation after failing to remove them all through phagocytosis. 

IHR is caused by several things. One of these is called a type I hypersensitivity reaction which happens when certain proteins (allergens) in things like cats, dust mites and drugs cause the body to make too much of a kind of protein called IgE. Another thing that can cause it are type II hypersensitivity reactions where different blood groups may lead to transfusion reactions through antigens on red cell membranes or erythrocyte membrane proteins. Then there’s also what’s known as type III hypersensitivity reactions which result from chronic infections or autoimmune diseases and cause complex immune system diseases such as vasculitis or glomerulonephritis. Finally, penicillin which is an example of an antigen can cause any type of hypersensitivity reaction including anaphylactic shock hemolytic anemia serum sickness. 

IHR prognosis is determined by severity of the disorders, the level of inflammation and tissue destruction and the effectiveness of the treatments available. Myasthenia gravis has a slow progression with 5 years survival rate of 68% for those who are affected. SLE 80% survival is recorded at 15 years if treated accordingly. In infancy atopic eczema is most severe but gets better as one grows older while allergic bronchial asthma has a poor prognosis. Good prognosis is attained for other allergic diseases like food or drug allergies, latex allergy conjunctivitis (eye) allergies rhinitis (nose) allergies among others once the causatives are identified Monoclonal antibodies targeting IgE have been found to improve the patient’s condition, but their accessibility proves difficult due to high costs involved in their acquisition. 

The diagnosis of the allergic reaction depends on the affected organ systems. 

Anaphylaxis 

People who have anaphylactic shock might feel itchy all over their body, especially on their skin, dizzy or light-headed, sweaty. They may have trouble breathing, have stomach pain like cramps (colic), vomit suddenly, or even collapse as if they were dead. Usually these begin within minutes of coming into contact with the thing that someone is allergic to but sometimes they can come back after a few hours. The person might not know what is causing their allergic reaction because they don’t know enough about allergies or because this happens far away from home where different things grow. It is important to think about new medicine someone started taking recently; insect bites people got any time recently; where someone has been working or living lately (dust, chemicals); and what people eat every day or rarely eat at all. Anaphylaxis that only happens after exercise could mean someone had eaten one kind of food or taken some drug before doing it. 

Allergic rhinoconjuctivitis 

Rhinoconjunctivitis can occur throughout the year because of exposure to any allergen in the air but most frequently takes place seasonally when certain plants release their pollens. It leads to symptoms such as stuffy or runny nose, sneezing, itchy eyes, nose, and palate. It may also cause itching which results in sore throat, coughing or constant throat clearing. If the allergic inflammation persists for a long time, then there might be chronic nasal blockage as well as sinusitis. 

Allergic asthma 

In 2007, the guidelines from NAEPP (National Asthma Education and Prevention Program) from NHLBI (National Heart, Lung, and Blood Institute) classified asthma into four different groups namely severe persistent, moderate persistent, mild persistent and intermittent. Severity is measured by the risk and impairment. Patients usually report symptoms like bronchoconstriction, coughing, wheezing and chest tightness. Prolonged exposure can lead to chronic changes in the airways. 

Angioedema/ Urticaria 

Urticaria can lead to wheals or hives, lasting about one day in one place. Foods, drugs, viral infections, or allergens can cause acute urticaria. Chronic urticaria persists for more than six weeks and usually occurs due to idiopathic causes. Swelling or angioedema of laryngopharynx leads to airway obstruction which causes breathing difficulties. This condition may be fatal. 

Atopic dermatitis 

This is frequent in children than adults which can occur due to exposure to environmental allergens or food. Patients report pruritis which causes scratching and exacerbation of lesions. In case of cracked lesions superinfection may occur due to Staphylococcal microbes. 

Allergies of GI tract 

Diarrhea, cramping in the abdomen, nausea and vomiting may be reported. Eosinophilic gastroenteritides is usually considered as the main symptom in GI allergies. 

Bronchial asthma, food allergy or allergic rhinitis or infections due to bacteria and viruses can be observed in type-I hypersensitivity reactions. The most severe kind of allergy, anaphylaxis is characterised by angioedema, hypotension, generalized rashes of skin, bronchospasm, loss of consciousness and abdominal cramps. 

Autoimmune hemolytic anemia, blood dyscrasia, immune thrombocytopenia may be reported in type-II hypersensitivity reactions. All these might occur due to rhesus incompatibility, drug history or multiple blood transfusions as reported by the patients.  

Immune complex mediated conditions like vasculitis, arthritis, serositis and glomerulonephrirtis may be manifested in type-III hypersensitivity reactions. Skin manifestations that can be observed due to photosensitivity include malar rash. Regular disease manifestations that can be observed are loss of weight, asthenia, and anorexia. 

The four different hypersensitivity reactions have specific treatment approaches. For type-I hypersensitivity reactions such as asthma, anaphylaxis, urticaria etc., acute management consists of antihistamines, corticosteroids, beta-agonists, epinephrine, and oxygen therapy. In case of type-II reactions, management involves identification and removal of allergens following symptomatic treatment and supportive care. For type-III reactions, reducing immune response and inflammation are necessary that includes treatment with corticosteroids, DMARDs and NSAIDS. For type-IV hypersensitivity reactions like tuberculin skin reactions, contact dermatitis, chronic transplant rejection, treatment includes use of anti-inflammatory medications, immunosuppressive agents etc. Educating patients to avoid substances that triggers allergic reactions is crucial in prevention and management of hypersensitivity reactions.  

Allergy and Immunology

To control hypersensitivity responses, modifying the surroundings is particularly necessary for individuals who have severe or long-term allergic reactions. These may encompass making the bedroom allergen-proof, using hypoallergenic casings, washing beddings on a weekly basis, changing carpets to hardwood, tile or linoleum floors, using HEPA filters and keeping humidity low. In addition, pet dander should not be allowed into the bedroom and cleaned frequently. Fixing leaks, cleaning water damage, and sealing cracks are some of the ways through which mold control can be achieved while pest control can be done by the same method. Moreover, indoor air quality can be improved by use of air purifiers with HEPA filters, maintaining HVAC systems and minimizing indoor plants. 

Allergy and Immunology

Epinephrine: This is used immediately in treatment of anaphylactic shock/anaphylaxis. It is available in the form of IM, IV, SC or ET preparations.  

Allergy and Immunology

Albuterol: It is a sympathomimetic drug that stimulates the beta-2 receptors which leads to bronchodilation. This is the first line of drug in treating bronchospasm related to asthma. 

Fluticasone/ Salmeterol inhaled: Salmeterol is a long-acting beta agonist which acts by stimulating the intracellular adenyl cyclase that results in elevated levels of cAMP that causes relaxation of smooth muscle. It also inhibits the release of chemicals of IHR from cells particularly from mast cells. 

Fluticasone is a difluorinated corticosteroid that has potent anti-inflammatory effects. It inhibits the secretion of histamines, leukotrienes, eicosanoids and multiple cell types like mast cells, basophils, eosinophils, neutrophils, macrophages, and lymphocytes responsible for asthmatic response. 

Budesonide and Formoterol:  Formoterol is a long acting and selective agonist of beta-2 adrenergic receptors. It is a locally acting bronchodilator with immediate onset of action. 

Budesonide is an anti-inflammatory corticosteroid with weak mineralocorticoid and strong glucocorticoid activity. 

Mometasone and Formoterol: Mometasone is a glucocorticoid that enhances the anti-inflammatory effects locally on the respiratory tract. 

Formoterol is a selective beta2 adrenergic agonist that is long-acting. It produces bronchodilator effects locally by stimulating the release of intracellular adenyl cyclase. 

Allergy and Immunology

Prednisone: This drug is thought to improve the delayed effects of anaphylactic reactions and might prevent biphasic anaphylaxis. 2mg/kg upto 30mg once daily can be considered as dosing for exacerbate asthma. 

Methylprednisone: This is a potent that has minimal to no mineralocorticoid activity. It controls inflammation by managing the rate of protein synthesis via suppression of PMNs and fibroblasts. 

Dexamethasone: This is also known to similarly to prednisone. Dose is 0.6mg/kg upto 16mg once a day for two days. 

Hydrocortisone: It is a glucocorticoid that evokes mild mineralocorticoid and moderate anti-inflammatory activities and prevents inflammation via controlling protein synthesis. 

Allergy and Immunology

Cetrizine: It is a selective inhibitor of histamine H1 receptor in GI tract, respiratory tract and blood vessels. It can be used as a one daily regimen. 

Fexofenadine: It also acts similar to cetirizine. It inhibits the physiological effects of histamines at H1 receptor. 

Loratidine/ Desloratidine: Both the drugs are long-acting antihistamines. They inhibit the physiological activity of histamines at H1 receptors.  

Azelastine/ Olopatadine intranasal: These are effective antihistamines administered intranasally. It can cause headache, nasal burning, and sedation. 

Allergy and Immunology

Ranitidine: this is mainly used in treating urticaria (chronic idiopathic). It is given concomitantly with H1 antagonists if symptoms were not relived with H1 antagonists alone. It is also an adjuvant in anaphylactic therapy. 

Famotidine: it is used in treating chronic idiopathic urticaria. 

Allergy and Immunology

Montelukast: This is a competitive and selective inhibitor of cysteinyl leukotriene receptors that are associated with inflammatory effects contributing asthmatic symptoms. 

Zafirlukast: It is a competitive antagonist of D4 and E4 leukotriene receptors and inhibits bronchoconstriction. 

Allergy and Immunology

Tacrolimus ointment: This drug decreases inflammation and itching through suppression of release of cytokines from the T cells. 

Pimecrolimus: This is a calcineurin inhibitor. It also inhibits the activation of T cells thereby blocks the release of inflammatory mediators. 

Allergy and Immunology

Omalizumab: This binds to free IgE and prevents IgE from binding to the IgE receptor on basophils and mast cells. It is known to show reduced allergic response in patients with peanut allergy. 

Mepolizumab: This inhibits the bioactivity of IL-5, a cytokine responsible for differentiation and growth, recruitment, activation, and survival of eosinophils. 

Duplimab: This monoclonal antibody binds to the subunit of IL-4R alpha inhibits the inflammatory responses that are induced by cytockines IL-3 and IL-4.  

Zileuton: This is an inhibitor of 5-lipoxygenase that inhibits the leukotrienes formation which leads to reduction in migration of eosinophils and neutrophils, capillary permeability, contraction of smooth muscles and aggregation of monocytes and neutrophils. 

Allergy and Immunology

Prevention/ deterrence: Avoiding the use if allergens in best way of prevention. Patients should always carry their medication with them. Allergen-specific immunotherapy should be practised. 

Patient education: Patients with known allergies should avoid the use of triggering substances in day-to-day life. Proper use of medications and maintenance of hygienic environments and keeping rescue medications helps to prevent the outbreak of allergies.