Frieda Shigwedha
Anastasia Aluvilu
The immune system is an integral part of human protection against diseases by fighting off invasive substances and infections.
However, sometimes it can cause a detrimental effect called hypersensitivity reactions.
A hypersensitivity reaction (or hypersensitivity) is an inappropriate or exaggerated response to an antigen or allergen produced by the immune system.
An antigen is any substance that causes the immune system to produce antibodies, whereas antibodies are proteins or immunoglobulins produced in response to the antigen to destroy the antigen.
An allergen is an antigen that causes allergies.
The confusion between the types of hypersensitivity reactions is very common and can lead to oversight or delay of the treatment, which at times requires timely administration.
This article explains the different types of hypersensitivity reactions in detail.
Broadly speaking, there are four (4) main classes of hypersensitivity reactions, usually classified based on the pathophysiology, onset of the reactions and the causative agents.
These factors are also important in the management and formulation of preventative actions.
Type I hypersensitivity reactions, also known as the immediate hypersensitivity reactions because they cause an immediate response, lasting up to 48-72 hours, are the most common hypersensitivity reactions.
There are two stages of type I hypersensitivity: the sensitisation stage and the effect stage.
In the sensitisation stage, the person encounters the antigen but does not experience any symptoms.
In the effect stage, the person’s exposure to the antigen results in the body recognising the antigen and producing a response that results in the usual allergic reaction symptoms.
These reactions occur when a subclass of antibodies, called immunoglobulin E (IgE), recognises an antigen or allergen and attaches itself to it.
By attaching to the antigen, the IgE activates a chain of reactions that result in the widespread of chemicals, including histamine.
The chemicals released cause dilatation of blood vessels, and smooth muscle spasms and are responsible for symptoms such as oedema, including swelling of the face (typically around eyes and mouth), rash and hives, difficulty in breathing due to spasm of the airways, abdominal cramps, vomiting and diarrhoea – and in serious cases, loss of consciousness.
The common antigens include pollen, various foods (e.g. milk, eggs, seafood, peas/beans nuts causing peanut allergy), mites, latex, bird and cat dander, medicines (sulpha allergy: penicillin and sulphonamides, local anaesthetics, salicylates), toxins (e.g. bee sting).
Anaphylaxis and allergic conditions (allergic rhinitis, allergic asthma and conjunctivitis) are examples of common type I reactions.
Treatment may include adrenaline, systemic glucocorticoids and antihistamines.
The cause of the hypersensitivity or the symptoms one presents will determine the course of treatment, e.g., emergency medical treatment with an immediate effect for severe symptoms.
Type II hypersensitivity reactions, also known as cytotoxic reactions, are antibody-mediated reactions, where immunoglobulins IgM and IgG mistakenly bind to the surface antigens of the cells in the body, causing healthy cells to die as they respond to the antigens, with a potential to cause long-term damage to cells and tissues.
These reactions can result in thrombocytopenia (low platelet count), haemolytic anaemia (abnormal breakdown of red blood cells), neutropenia (low white cell count) or several autoimmune reactions (when the body mistakenly attacks normal cells, e.g., Graves diseases, myasthenia gravis, lupus nephritis) but also responsible for non-autoimmune reactions such as transfusion reactions/serum sickness due to incompatibility and haemolytic disease of the newborn (erythroblastosis fetalis).
Serious drug reactions can also occur, caused by medicines such as penicillin, cephalosporin, sulphonamides, thiazides and methyldopa.
Treatment may include systemic glucocorticoids, cyclophosphamide and cyclosporine agents, intravenous immunoglobulin infusion and plasmapheresis.
Type III hypersensitivity reactions, also known as immune complex reactions, involve IgM and IgG antibodies bound to antigens in the blood.
These antibody-antigen complexes can precipitate and get stuck in certain locations, such as blood vessels in the skin, kidney and joints, where they activate a sequence of activities to cause local damage.
There is a large variety of diseases that can lead to type III hypersensitivity reactions, which include systemic lupus erythematosus, rheumatoid arthritis, serum sickness and small vessel vasculitis, usually presenting as raised, palpable (blood) discolouration of the skin.
Treatment may include systemic glucocorticoids, cyclophosphamide and cyclosporine agents, and intravenous immunoglobulin infusion.
Type IV hypersensitivity reactions, also known as delayed hypersensitivity reactions, usually occur 48-72 hours after exposure to the antigen.
Unlike the other three types of hypersensitivity reactions, the type IV hypersensitivity reactions do not involve antibodies, but rather T-cell lymphocytes.
A T-cell lymphocyte is a type of white blood cell, which when activated by an antigen, leads to the release of chemicals that destroy the target cells upon contact.
Examples of type IV hypersensitivity reactions include contact dermatitis, Steven-Johnson syndrome/toxic epidermal necrolysis, which may be caused by exposure to poison ivy, certain metals (e.g., nickel), and medicines such as nevirapine, co-trimoxazole (trimethoprim/sulfamethoxazole), thiazides, methyldopa, and anticonvulsants (medicines used in epilepsy).
A general rule is that if an individual has reacted to an antigen – be it pollen, food or medicine resulting in a hypersensitivity reaction, the class or family that the antigen belongs to must be avoided in that individual in the future as similar events are expected to occur – and at times – at a serious degree compared to the previous episode.
Individuals are advised to avoid exposure to insects and environments with high humidity.
The bedroom should be cleaned, mattress covers should be used, and bed linens should be washed regularly.
Pets, including cats and dogs, are often the source of allergens and should not be in proximity to the affected individuals, nor should allergen-containing plants and flowers.
Healthcare professionals can advise individuals with or prone to allergies about environmental control at home and workplaces.
* Anastasia Aluvilu and Frieda Shigwedha are medicines information and safety pharmacists at the Therapeutics Information and Pharmacovigilance Centre, Namibia Medicines Regulatory Council.